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Sample records for nuclear jungle compartmentalization

  1. Demonstration of nuclear compartmentalization of glutathione in hepatocytes.

    PubMed Central

    Bellomo, G; Vairetti, M; Stivala, L; Mirabelli, F; Richelmi, P; Orrenius, S

    1992-01-01

    The intracellular distribution of glutathione (GSH) in cultured hepatocytes has been investigated by using the compound monochlorobimane (BmCl), which interacts specifically with GSH to form a highly fluorescent adduct. Image analysis of BmCl-labeled hepatocytes predominantly localized the fluorescence in the nucleus; the nuclear/cytoplasmic concentration gradient was approximately three. This concentration gradient was collapsed by treatment of the cells with ATP-depleting agents. The uneven distribution of BmCl fluorescence was not attributable to (i) nonspecific interaction of BmCl with protein sulfhydryl groups, (ii) any selective nuclear localization of the GSH transferase(s) catalyzing formation of the GSH-BmCl conjugate, or (iii) any apparent alterations in cell morphology from culture conditions, suggesting that this distribution did, indeed, reflect a nuclear compartmentalization of GSH. That the nuclear pool of GSH was found more resistant to depletion by several agents than the cytoplasmic pool supports the assumption that GSH is essential in protecting DNA and other nuclear structures from chemical injury. Images PMID:1584774

  2. Nuclear compartmentalization of the v-myb oncogene product.

    PubMed Central

    Boyle, W J; Lampert, M A; Li, A C; Baluda, M A

    1985-01-01

    Nuclei obtained from chicken leukemic myeloblasts transformed by avian myeloblastosis virus were fractionated into various subnuclear compartments, which were then analyzed by specific immunoprecipitation for the presence of the leukemogenic product, p48v-myb, of the viral oncogene. In cells labeled for 30 or 60 min with L-[35S]methionine and in unlabeled exponentially dividing leukemic cells analyzed by Western blotting, p48v-myb was detected within the nucleoplasm (29 +/- 9% [standard deviation] of the total), chromatin (7 +/- 4%), and lamina-nuclear matrix (64 +/- 9%). Also, in myeloblasts analyzed by immunofluorescence during mitosis, p48v-myb appeared to be dispersed through the cell like the lamina-nuclear matrix complex. Strong attachment to the nuclear matrix-lamina complex suggests that p48v-myb may be involved in DNA replication or transcription or both. Images PMID:3018495

  3. A global comparison between nuclear and cytosolic transcriptomes reveals differential compartmentalization of alternative transcript isoforms

    PubMed Central

    Chen, Liang

    2010-01-01

    Transcriptome analyses have typically disregarded nucleocytoplasmic differences. This approach has ignored some post-transcriptional regulations and their effect on the ultimate protein expression levels. Despite a longstanding interest in the differences between the nuclear and cytosolic transcriptomes, it is only recently that data have become available to study such differences and their associated features on a genome-wide scale. Here, we compared the nuclear and cytosolic transcriptomes of HepG2 and HeLa cells. HepG2 and HeLa cells vary significantly in the differential compartmentalization of their transcript isoforms, indicating that nucleocytoplasmic compartmentalization is a cell-specific characteristic. The differential compartmentalization is manifested at the transcript isoform level instead of the gene level because alternative isoforms of one gene can display different nucleocytoplasmic distributions. The isoforms enriched in the cytosol tend to have more introns and longer introns in their pre-mRNAs. They have more functional RNA folds and unique exons in the 3′ regions. These isoforms are more conserved than the isoforms enriched in the nucleus. Surprisingly, the presence of microRNAs does not have a significant impact on the nucleocytoplasmic distribution of their target isoforms. In contrast, nonsense-mediated decay is significantly more associated with the isoforms enriched in the nucleus than those enriched in the cytosol. PMID:19969546

  4. Substrate-induced Nuclear Export and Peripheral Compartmentalization of Hepatic Glucokinase Correlates with Glycogen Deposition

    PubMed Central

    Shiota, Masa; Knobel, Susan M.; Piston, David W.; Cherrington, Alan D.; Magnuson, Mark A.

    2001-01-01

    Hepatic glucokinase (GK) is acutely regulated by binding to its nuclear-anchored regulatory protein (GKRP). Although GK release by GKRP is tightly coupled to the rate of glycogen synthesis, the nature of this association is obscure. To gain insight into this coupling mechanism under physiological stimulating conditions in primary rat hepatocytes, we analyzed the subcellular distribution of GK and GKRP with immunofluorescence, and glycogen deposition with glycogen cytochemical fluorescence, using confocal microscopyand quantitative image analysis. Following stimulation, a fraction of the GK signal translocated from the nucleus to the cytoplasm. The reduction in the nuclear to cytoplasmic ratio of GK, an index of nuclear export, correlated with a >50% increase in glycogen cytochemical fluorescence over a 60min stimulation period. Furthermore, glycogen accumulation was initially deposited in a peripheral pattern in hepatocytes similar to that of GK. These data suggest that a compartmentalization exists of both active GK and the initial sites of glycogen deposition at the hepatocyte surface. PMID:12369705

  5. Compositional compartmentalization and compositional patterns in the nuclear genomes of plants.

    PubMed Central

    Salinas, J; Matassi, G; Montero, L M; Bernardi, G

    1988-01-01

    We report here results which indicate (i) that the nuclear genomes of angiosperms is characterized by a compositional compartmentalization and an isochore structure; and (ii) that the nuclear genomes of some Gramineae exhibit strikingly different compositional patterns compared to those of many dicots. Indeed, the compositional distribution of nuclear DNA molecules (in the 50-100 Kb size range) from three dicots (pea, sunflower and tobacco) and three monocots (maize, rice and wheat) were found to be centered around lower (41%) and higher (45% for rice, 48% for maize and wheat) GC levels, respectively (and to trail towards even higher GC values in maize and wheat). Experiments on gene localization in density gradient fractions showed a remarkable compositional homogeneity in vast (greater than 100-200 Kb) regions surrounding the genes. On the other hand, the compositional distribution of coding sequences (GenBank and literature data) from dicots (several orders) was found to be narrow, symmetrical and centered around 46% GC, that from monocots (essentially barley, maize and wheat) to be broad, asymmetrical and characterized by an upward trend towards high GC values, with the majority of sequences between 60 and 70% GC. Introns exhibited a similar compositional distribution, but lower GC levels, compared to exons from the same genes. Images PMID:3380684

  6. Generation of compartmentalized pressure by a nuclear piston governs cell motility in a 3D matrix.

    PubMed

    Petrie, Ryan J; Koo, Hyun; Yamada, Kenneth M

    2014-08-29

    Cells use actomyosin contractility to move through three-dimensional (3D) extracellular matrices. Contractility affects the type of protrusions cells use to migrate in 3D, but the mechanisms are unclear. In this work, we found that contractility generated high-pressure lobopodial protrusions in human cells migrating in a 3D matrix. In these cells, the nucleus physically divided the cytoplasm into forward and rear compartments. Actomyosin contractility with the nucleoskeleton-intermediate filament linker protein nesprin-3 pulled the nucleus forward and pressurized the front of the cell. Reducing expression of nesprin-3 decreased and equalized the intracellular pressure. Thus, the nucleus can act as a piston that physically compartmentalizes the cytoplasm and increases the hydrostatic pressure between the nucleus and the leading edge of the cell to drive lamellipodia-independent 3D cell migration. PMID:25170155

  7. DNA precursor compartmentation in mammalian cells: metabolic and antimetabolic studies of nuclear and mitochondrial DNA synthesis

    SciTech Connect

    Bestwick, R.K.

    1983-01-01

    HeLa cells were used for the quantitation of cellular and mitochondrial deoxyribonucleoside triphosphate (dNTP) and ribonucleoside triphosphate (rNTP) pools and of changes in pools in response to treatment with the antimetabolites methotrexate (mtx) and 5-fluorodeoxyuridine (FUdR). Use of an enzymatic assay of dNTPs and of improved nucleotide extraction methods allowed quantitation of mitochondrial dNTP pools. All four mitochondrial dNTP pools expand following treatment with mtx or FUdR whereas cellular dTTP and dGTP pools are depleted. Mitochrondrial rNTP pools were also found to expand in response to these antimetabolites. Mouse L-cells were used to determine the relative contributions of an exogenously supplied precursor to nuclear and mitochrondrial DNA replication. Cells were labeled to near steady state specific activities with /sup 32/P-orthophosphate and subsequently labeled with (/sup 3/H)uridine, a general pyrimidine precursor, in the continuing presence of /sup 32/P. Deoxyribonucleoside monophosphates derived from these DNAs were separated by HPLC and the /sup 3/H//sup 32/P ratio in each pyrimidine determined. The dCMP residues in mitochondrial DNA (mtDNA) were found to be derived exclusively from the exogenous supplied uridine. The dTMP residues from nuclear and mtDNA and the dCMP residues from nuclear DNA were seen to be synthesized partly from exogenous sources and partly from other sources, presumably de novo pyrimidine synthesis.

  8. Compartmentalization and Functionality of Nuclear Disorder: Intrinsic Disorder and Protein-Protein Interactions in Intra-Nuclear Compartments

    PubMed Central

    Meng, Fanchi; Na, Insung; Kurgan, Lukasz; Uversky, Vladimir N.

    2015-01-01

    The cell nucleus contains a number of membrane-less organelles or intra-nuclear compartments. These compartments are dynamic structures representing liquid-droplet phases which are only slightly denser than the bulk intra-nuclear fluid. They possess different functions, have diverse morphologies, and are typically composed of RNA (or, in some cases, DNA) and proteins. We analyzed 3005 mouse proteins localized in specific intra-nuclear organelles, such as nucleolus, chromatin, Cajal bodies, nuclear speckles, promyelocytic leukemia (PML) nuclear bodies, nuclear lamina, nuclear pores, and perinuclear compartment and compared them with ~29,863 non-nuclear proteins from mouse proteome. Our analysis revealed that intrinsic disorder is enriched in the majority of intra-nuclear compartments, except for the nuclear pore and lamina. These compartments are depleted in proteins that lack disordered domains and enriched in proteins that have multiple disordered domains. Moonlighting proteins found in multiple intra-nuclear compartments are more likely to have multiple disordered domains. Protein-protein interaction networks in the intra-nuclear compartments are denser and include more hubs compared to the non-nuclear proteins. Hubs in the intra-nuclear compartments (except for the nuclear pore) are enriched in disorder compared with non-nuclear hubs and non-nuclear proteins. Therefore, our work provides support to the idea of the functional importance of intrinsic disorder in the cell nucleus and shows that many proteins associated with sub-nuclear organelles in nuclei of mouse cells are enriched in disorder. This high level of disorder in the mouse nuclear proteins defines their ability to serve as very promiscuous binders, possessing both large quantities of potential disorder-based interaction sites and the ability of a single such site to be involved in a large number of interactions. PMID:26712748

  9. Functional redundancy in the nuclear compartmentalization of the late-replicating genome

    PubMed Central

    Ragoczy, Tobias; Telling, Agnes; Scalzo, David; Kooperberg, Charles; Groudine, Mark

    2014-01-01

    The eukaryotic nucleus is structurally and functionally organized, as reflected in the distribution of its protein and DNA components. The genome itself is segregated into euchromatin and heterochromatin that replicate in a distinct spatio-temporal manner. We used a combination of fluorescence in situ hybridization (FISH) and DamID to investigate the localization of the early and late replicating components of the genome in a lymphoblastoid cell background. Our analyses revealed that the bulk of late replicating chromatin localizes to the nuclear peripheral heterochromatin (PH) in a chromosome size and gene density dependent manner. Late replicating DNA on small chromosomes exhibits a much lower tendency to localize to PH and tends to associate with alternate repressive subcompartments such as pericentromeric (PCH) and perinucleolar heterochromatin (PNH). Furthermore, multicolor FISH analysis revealed that late replicating loci, particularly on the smaller chromosomes, may associate with any of these 3 repressive subcompartments, including more than one at the same time. These results suggest a functional equivalence or redundancy among the 3 subcompartments. Consistent with this notion, disruption of nucleoli resulted in an increased association of late replicating loci with peripheral heterochromatin. Our analysis reveals that rather than considering the morphologically distinct PH, PCH and PNH as individual subcompartments, they should be considered in aggregate as a functional compartment for late replicating chromatin. PMID:25493640

  10. How Should We Teach "The Jungle"?

    ERIC Educational Resources Information Center

    Phelps, Christopher

    2006-01-01

    Upton Sinclair's "The Jungle" describes a callous America in which the dollar trumps justice. It famously exposed the American meatpacking industry's loathsome practices and prompted federal consumer-protection laws. It is, however, primarily a sympathetic sketch of the foreign born, those fabled "masses yearning to breathe free" that Americans…

  11. Estimate of FDG excretion by means of compartmental analysis and ant colony optimization of nuclear medicine data.

    PubMed

    Garbarino, Sara; Caviglia, Giacomo; Brignone, Massimo; Massollo, Michela; Sambuceti, Gianmario; Piana, Michele

    2013-01-01

    [(18)F]fluoro-2-deoxy-D-glucose (FDG) is one of the most utilized tracers for positron emission tomography (PET) applications in oncology. FDG-PET relies on higher glycolytic activity in tumors compared to normal structures as the basis of image contrast. As a glucose analog, FDG is transported into malignant cells which typically exhibit an increased radioactivity. However, different from glucose, FDG is not reabsorbed by the renal system and is excreted to the bladder. The present paper describes a novel computational method for the quantitative assessment of this excretion process. The method is based on a compartmental analysis of FDG-PET data in which the excretion process is explicitly accounted for by the bladder compartment and on the application of an ant colony optimization (ACO) algorithm for the determination of the tracer coefficients describing the FDG transport effectiveness. The validation of this approach is performed by means of both synthetic data and real measurements acquired by a PET device for small animals (micro-PET). Possible oncological applications of the results are discussed in the final section. PMID:24191175

  12. Nuclear Compartmentalization of Serine Racemase Regulates D-Serine Production: IMPLICATIONS FOR N-METHYL-D-ASPARTATE (NMDA) RECEPTOR ACTIVATION.

    PubMed

    Kolodney, Goren; Dumin, Elena; Safory, Hazem; Rosenberg, Dina; Mori, Hisashi; Radzishevsky, Inna; Radzishevisky, Inna; Wolosker, Herman

    2015-12-25

    D-Serine is a physiological co-agonist that activates N-methyl D-aspartate receptors (NMDARs) and is essential for neurotransmission, synaptic plasticity, and behavior. D-Serine may also trigger NMDAR-mediated neurotoxicity, and its dysregulation may play a role in neurodegeneration. D-Serine is synthesized by the enzyme serine racemase (SR), which directly converts L-serine to D-serine. However, many aspects concerning the regulation of D-serine production under physiological and pathological conditions remain to be elucidated. Here, we investigate possible mechanisms regulating the synthesis of D-serine by SR in paradigms relevant to neurotoxicity. We report that SR undergoes nucleocytoplasmic shuttling and that this process is dysregulated by several insults leading to neuronal death, typically by apoptotic stimuli. Cell death induction promotes nuclear accumulation of SR, in parallel with the nuclear translocation of GAPDH and Siah proteins at an early stage of the cell death process. Mutations in putative SR nuclear export signals (NESs) elicit SR nuclear accumulation and its depletion from the cytosol. Following apoptotic insult, SR associates with nuclear GAPDH along with other nuclear components, and this is accompanied by complete inactivation of the enzyme. As a result, extracellular D-serine concentration is reduced, even though extracellular glutamate concentration increases severalfold. Our observations imply that nuclear translocation of SR provides a fail-safe mechanism to prevent or limit secondary NMDAR-mediated toxicity in nearby synapses. PMID:26553873

  13. Lysine-specific demethylase-1 (LSD1) is compartmentalized at nuclear chromocenters in early post-mitotic cells of the olfactory sensory neuronal lineage.

    PubMed

    Kilinc, Seda; Savarino, Alyssa; Coleman, Julie H; Schwob, James E; Lane, Robert P

    2016-07-01

    Mammalian olfaction depends on the development of specialized olfactory sensory neurons (OSNs) that each express one odorant receptor (OR) protein from a large family of OR genes encoded in the genome. The lysine-specific demethylase-1 (LSD1) protein removes activating H3K4 or silencing H3K9 methylation marks at gene promoters and is required for proper OR regulation. We show that LSD1 protein exhibits variable organization within nuclei of developing OSNs, and tends to consolidate into a single dominant compartment at the edges of chromocenters within nuclei of early post-mitotic cells of the mouse olfactory epithelium (MOE). Using an immortalized cell line derived from developing olfactory placode, we show that consolidation of LSD1 appears to be cell-cycle regulated, with a peak occurrence in early G1. LSD1 co-compartmentalizes with CoREST, a protein known to collaborate with LSD1 to carry out a variety of chromatin-modifying functions. We show that LSD1 compartments co-localize with 1-3 OR loci at the exclusion of most OR genes, and commonly associate with Lhx2, a transcription factor involved in OR regulation. Together, our data suggests that LSD1 is sequestered into a distinct nuclear space that might restrict a histone-modifying function to a narrow developmental time window and/or range of OR gene targets. PMID:26947098

  14. SUMO-dependent compartmentalization in promyelocytic leukemia protein nuclear bodies prevents the access of LRH-1 to chromatin.

    PubMed

    Chalkiadaki, Angeliki; Talianidis, Iannis

    2005-06-01

    Posttranslational modification by SUMO elicits a repressive effect on many transcription factors. In principle, sumoylation may either influence transcription factor activity on promoters, or it may act indirectly by targeting the modified factors to specific cellular compartments. To provide direct experimental evidence for the above, not necessarily mutually exclusive models, we analyzed the role of SUMO modification on the localization and the activity of the orphan nuclear receptor LRH-1. We demonstrate, by using fluorescence resonance energy transfer (FRET) and fluorescence recovery after photobleaching (FRAP) assays, that sumoylated LRH-1 is exclusively localized in promyelocytic leukemia protein (PML) nuclear bodies and that this association is a dynamic process. Release of LRH-1 from nuclear bodies correlated with its desumoylation, pointing to the pivotal role of SUMO conjugation in keeping LRH-1 in these locations. SUMO-dependent shuttling of LRH-1 into PML bodies defines two spatially separated pools of the protein, of which only the soluble, unmodified one is associated with actively transcribed target genes. The results suggest that SUMO-PML nuclear bodies may primarily function as dynamic molecular reservoirs, controlling the availability of certain transcription factors to active chromatin domains. PMID:15923626

  15. Job Hunting? It's a Jungle out There! Jungle Survival Guide II.

    ERIC Educational Resources Information Center

    Florida State Dept. of Education, Tallahassee. Div. of Vocational, Adult, and Community Education.

    This illustrated, jungle-theme book plans a job search. There are three major sections in the book: (1) plan your safari; (2) where to look for jobs; and (3) making contact. Section one includes information on resumes, references, official papers needed for a job, and 11 ideas to help find job openings. Section two suggests finding jobs in state…

  16. A Five-Species Jungle Game

    PubMed Central

    Kang, Yibin; Pan, Qiuhui; Wang, Xueting; He, Mingfeng

    2016-01-01

    In this paper, we investigate the five-species Jungle game in the framework of evolutionary game theory. We address the coexistence and biodiversity of the system using mean-field theory and Monte Carlo simulations. Then, we find that the inhibition from the bottom-level species to the top-level species can be critical factors that affect biodiversity, no matter how it is distributed, whether homogeneously well mixed or structured. We also find that predators’ different preferences for food affect species’ coexistence. PMID:27332995

  17. Compartmentalization of Decay in Trees.

    ERIC Educational Resources Information Center

    Shigo, Alex L.

    1985-01-01

    Unlike animals, which heal, trees compartmentalize by setting boundaries that resist the spread of invading microorganisms. Discusses the creation of new walls by anatomical and chemical means in response to death of a branch or pruning. Points out that genetic control of compartmentalization has resulted from evolution of resistant species. (DH)

  18. Physiology Education and the Linguistic Jungle of Science

    ERIC Educational Resources Information Center

    Nordquist, Lina

    2008-01-01

    Life sciences can be complicated enough without getting into the names of all its Dalton-scale participants. For many students, composing a project plan or writing a paper is rather like learning a foreign language. In this article, the author argues that there is a linguistic jungle of science, and it may well discourage students from pursuing a…

  19. Cellular compartmentalization of secondary metabolism

    PubMed Central

    Kistler, H. Corby; Broz, Karen

    2015-01-01

    Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g., amino acids, acetyl CoA, NADPH), enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported. PMID:25709603

  20. Identifying compartmentalization in gas reservoirs

    SciTech Connect

    Junkin, J.; Cooper, K.; Sippel, M.

    1997-01-01

    Compartmentalization as a function of depositional systems is now recognized as a common type of reservoir heterogeneity that limits recovery from oil and gas reservoirs. US Department of Energy (DOE) estimates indicate that substantial quantities of gas resources will not be recovered from presently identified reservoirs under historic development practices. The Secondary Natural Gas Recovery (SGR) project sponsored by the Gas Research Institute (GRI), state of Texas and DOE quantified compartmentalization over intervals as large as 2,000 feet in several different fluvial deltaic reservoirs. Early recognition of compartmentalized behavior can be used to pursue a more rapid development plan including efficient well spacing and elimination of redundant wells. Three classes of reservoir compartment sizes were delineated in the SGR project using methods discussed in this article. Forward stochastic modeling of gas recovery from these compartment-size classes established well spacing requirements that would yield maximum gas contact efficiency. The presence of reservoir compartmentalization was also shown to correlate with reserve growth. Also, those reservoirs classified as having smaller compartment sizes exhibited the greatest reserve growth potential. Utilization of tools, such as personal computer-based methods discussed, enables better engineering interpretation of actual field behavior. Some of these tools require minimal production data, which is readily available on CD-ROM or via modem at very low cost.

  1. Compartmental Modeling in Emission Tomography

    NASA Astrophysics Data System (ADS)

    Lammertsma, Adriaan A.

    This chapter provides an overview of the basic principles of compartmental modeling as it is being applied to the quantitative analysis of positron emission tomography (PET) studies. Measurement of blood flow (perfusion) is used as an example of a single tissue compartment model and receptor studies are discussed in relation to a two tissue compartment model. Emphasis is placed on the accurate measurement of both arterial whole blood and metabolite-corrected plasma input functions. Reference tissue models are introduced as a noninvasive tool to investigate neuroreceptor studies. Finally, parametric methods are introduced in which calculations are performed at a voxel level.

  2. Multiple maternal origins of chickens: out of the Asian jungles.

    PubMed

    Liu, Yi-Ping; Wu, Gui-Sheng; Yao, Yong-Gang; Miao, Yong-Wang; Luikart, Gordon; Baig, Mumtaz; Beja-Pereira, Albano; Ding, Zhao-Li; Palanichamy, Malliya Gounder; Zhang, Ya-Ping

    2006-01-01

    Domestic chickens have long been important to human societies for food, religion, entertainment, and decorative uses, yet the origins and phylogeography of chickens through Eurasia remain uncertain. Here, we assessed their origins and phylogeographic history by analyzing the mitochondrial DNA hypervariable segment I (HVS-I) for 834 domestic chickens (Gallus gallus domesticus) across Eurasia as well as 66 wild red jungle fowls (Gallus gallus) from Southeast Asia and China. Phylogenetic analyses revealed nine highly divergent mtDNA clades (A-I) in which seven clades contained both the red jungle fowls and domestic chickens. There was no breed-specific clade in the chickens. The clades A, B, and E are distributed ubiquitously in Eurasia, while the other clades were restricted to South and Southeast Asia. Clade C was mainly distributed in Japan and Southeast China, while clades F and G were exclusive to Yunnan, China. The geographic distribution of clade D was closely related to the distribution of the pastime of cock fighting. Statistical tests detect population expansion within each subclade. These distinct distribution patterns and expansion signatures suggest that different clades may originate from different regions, such as Yunnan, South and Southwest China and/or surrounding areas (i.e., Vietnam, Burma, and Thailand), and the Indian subcontinent, respectively, which support the theory of multiple origins in South and Southeast Asia. PMID:16275023

  3. Current Ideas about Prebiological Compartmentalization

    PubMed Central

    Monnard, Pierre-Alain; Walde, Peter

    2015-01-01

    Contemporary biological cells are highly sophisticated dynamic compartment systems which separate an internal volume from the external medium through a boundary, which controls, in complex ways, the exchange of matter and energy between the cell’s interior and the environment. Since such compartmentalization is a fundamental principle of all forms of life, scenarios have been elaborated about the emergence of prebiological compartments on early Earth, in particular about their likely structural characteristics and dynamic features. Chemical systems that consist of potentially prebiological compartments and chemical reaction networks have been designed to model pre-cellular systems. These systems are often referred to as “protocells”. Past and current protocell model systems are presented and compared. Since the prebiotic formation of cell-like compartments is directly linked to the prebiotic availability of compartment building blocks, a few aspects on the likely chemical inventory on the early Earth are also summarized. PMID:25867709

  4. Current Ideas about Prebiological Compartmentalization.

    PubMed

    Monnard, Pierre-Alain; Walde, Peter

    2015-01-01

    Contemporary biological cells are highly sophisticated dynamic compartment systems which separate an internal volume from the external medium through a boundary, which controls, in complex ways, the exchange of matter and energy between the cell's interior and the environment. Since such compartmentalization is a fundamental principle of all forms of life, scenarios have been elaborated about the emergence of prebiological compartments on early Earth, in particular about their likely structural characteristics and dynamic features. Chemical systems that consist of potentially prebiological compartments and chemical reaction networks have been designed to model pre-cellular systems. These systems are often referred to as "protocells". Past and current protocell model systems are presented and compared. Since the prebiotic formation of cell-like compartments is directly linked to the prebiotic availability of compartment building blocks, a few aspects on the likely chemical inventory on the early Earth are also summarized. PMID:25867709

  5. Protocell design through modular compartmentalization.

    PubMed

    Miller, David; Booth, Paula J; Seddon, John M; Templer, Richard H; Law, Robert V; Woscholski, Rudiger; Ces, Oscar; Barter, Laura M C

    2013-10-01

    De novo synthetic biological design has the potential to significantly impact upon applications such as energy generation and nanofabrication. Current designs for constructing organisms from component parts are typically limited in scope, as they utilize a cut-and-paste ideology to create simple stepwise engineered protein-signalling pathways. We propose the addition of a new design element that segregates components into lipid-bound 'proto-organelles', which are interfaced with response elements and housed within a synthetic protocell. This design is inspired by living cells, which utilize multiple types of signalling molecules to facilitate communication between isolated compartments. This paper presents our design and validation of the components required for a simple multi-compartment protocell machine, for coupling a light transducer to a gene expression system. This represents a general design concept for the compartmentalization of different types of artificial cellular machinery and the utilization of non-protein signal molecules for signal transduction. PMID:23925982

  6. Compartmentalization and Organelle Formation in Bacteria

    PubMed Central

    Cornejo, Elias; Abreu, Nicole; Komeili, Arash

    2015-01-01

    A number of bacterial species rely on compartmentalization to gain specific functionalities that will provide them with a selective advantage. Here, we will highlight several of these modes of bacterial compartmentalization with an eye towards describing the mechanisms of their formation and their evolutionary origins. Spore formation in Bacillus subtilis, outer membrane biogenesis in Gram-negative bacteria and protein diffusion barriers of Caulobacter crescentus will be used to demonstrate the physical, chemical and compositional remodeling events that lead to compartmentalization. In addition, magnetosomes and carboxysomes will serve as models to examine the interplay between cytoskeletal systems and the subcellular positioning of organelles. PMID:24440431

  7. Jungle Computing: Distributed Supercomputing Beyond Clusters, Grids, and Clouds

    NASA Astrophysics Data System (ADS)

    Seinstra, Frank J.; Maassen, Jason; van Nieuwpoort, Rob V.; Drost, Niels; van Kessel, Timo; van Werkhoven, Ben; Urbani, Jacopo; Jacobs, Ceriel; Kielmann, Thilo; Bal, Henri E.

    In recent years, the application of high-performance and distributed computing in scientific practice has become increasingly wide spread. Among the most widely available platforms to scientists are clusters, grids, and cloud systems. Such infrastructures currently are undergoing revolutionary change due to the integration of many-core technologies, providing orders-of-magnitude speed improvements for selected compute kernels. With high-performance and distributed computing systems thus becoming more heterogeneous and hierarchical, programming complexity is vastly increased. Further complexities arise because urgent desire for scalability and issues including data distribution, software heterogeneity, and ad hoc hardware availability commonly force scientists into simultaneous use of multiple platforms (e.g., clusters, grids, and clouds used concurrently). A true computing jungle.

  8. Tick fauna of Malaysian red jungle fowl (Gallus gallus) in Bangi, Malaysia

    PubMed Central

    Konto, M.; Fufa, G. I.; Zakaria, A.; Tukur, S. M.; Watanabe, M.; Ola-Fadunsin, S. D.; Khan, M. S.; Shettima, Y. M.; Babjee, S. M. A.

    2015-01-01

    Aim: The red jungle fowl is generally considered as one of the endangered Asian wild Galleopheasants due to man-made encroachment of their habitats, coupled with the effect of disease and disease causing organisms like ticks and tick-borne infections. This study aimed to determine the tick fauna of the red jungle fowl and their predilection sites based on developmental stages. Materials and Methods: A total of 33 jungle fowls were sampled for this study from Bangi area of Selangor State, Peninsular Malaysian. The birds were captured using a locally made trap made-up of loops and bites. Ticks present on their bodies were detached using fine forceps and identified morphologically under a dissecting microscope. Results: 91% of the jungle fowls were infested with ticks, all of which belongs to the species Haemaphysalis wellingtoni. The ear region appeared to be the most common predilection site (63%) for all the developmental stages in which the larval stages are solely restricted to that region. Nymphal and adult stages were distributed on the comb, wattle, and facial region in addition to the ear region. Conclusion: This study was the first in its kind and showed a high prevalence of tick infestation among jungle fowls. H. wellingtoni was known to be a vector in transmission of many tick-borne pathogens. Therefore, there is the need for further investigation to identify the various pathogens associated with this tick. PMID:27047012

  9. Outbreak of human rabies in the Peruvian jungle.

    PubMed

    Lopez, A; Miranda, P; Tejada, E; Fishbein, D B

    1992-02-15

    Transmission of rabies to man by vampire bats has been known for 60 years but there have been few reports of the features of rabies transmitted in this way. These aspects of the disease were investigated during an outbreak in Peru in early 1990. Between Jan 1 and April 30, 1990, 29 (5%) of 636 residents of the two rural communities in the Amazon Jungle in Peru acquired an illness characterised by hydrophobia, fever, and headache and died shortly thereafter. A census in one of the two towns revealed that the proportion affected was significantly higher for 5-14 year olds (17%) than for other age-groups (p less than 10(-5). Interviews conducted with 23 of the patients or their families revealed that 22 (96%) had a history of bat bite, compared with 66 (22%) of 301 community members who remained healthy (p less than 10(-6). A rabies virus strain identical to those isolated from vampire bats (Desmodus rotundus) was isolated from the brain of the only person on whom necropsy could be done. Because of the extreme isolation of this and other communities affected by bat-transmitted rabies, preventive measures should be directed at decreasing the risk of nocturnal exposure to bats by bat proofing dwellings or use of mosquito nets and at prompt wound care. Rabies pre-exposure or postexposure vaccination is clearly indicated, but may not be feasible in these isolated populations. PMID:1346669

  10. Jesus and Maria in the Jungle: An Essay on Possibility and Constraint in the Third-Shift Third Space

    ERIC Educational Resources Information Center

    Bruna, Katherine Richardson

    2009-01-01

    One hundred years ago, Upton Sinclair, in "The Jungle," exposed the deplorable working conditions of eastern European immigrants in the meatpacking houses of Chicago. The backdrop of this article is the new Jungle of the 21st century--the hog plants of the rural Midwest. Here I speak to the lives of the Mexican workers they employ, and, more…

  11. Compartmentalized storage tank for electrochemical cell system

    NASA Technical Reports Server (NTRS)

    Piecuch, Benjamin Michael (Inventor); Dalton, Luke Thomas (Inventor)

    2010-01-01

    A compartmentalized storage tank is disclosed. The compartmentalized storage tank includes a housing, a first fluid storage section disposed within the housing, a second fluid storage section disposed within the housing, the first and second fluid storage sections being separated by a movable divider, and a constant force spring. The constant force spring is disposed between the housing and the movable divider to exert a constant force on the movable divider to cause a pressure P1 in the first fluid storage section to be greater than a pressure P2 in the second fluid storage section, thereby defining a pressure differential.

  12. Mitochondrial RNA granules: Compartmentalizing mitochondrial gene expression.

    PubMed

    Jourdain, Alexis A; Boehm, Erik; Maundrell, Kinsey; Martinou, Jean-Claude

    2016-03-14

    In mitochondria, DNA replication, gene expression, and RNA degradation machineries coexist within a common nondelimited space, raising the question of how functional compartmentalization of gene expression is achieved. Here, we discuss the recently characterized "mitochondrial RNA granules," mitochondrial subdomains with an emerging role in the regulation of gene expression. PMID:26953349

  13. Compartmentalized Platforms for Neuro-pharmacological Research

    PubMed Central

    Jadhav, Amol D.; Wei, Li; Shi, Peng

    2016-01-01

    Dissociated primary neuronal cell culture remains an indispensable approach for neurobiology research in order to investigate basic mechanisms underlying diverse neuronal functions, drug screening and pharmacological investigation. Compartmentalization, a widely adopted technique since its emergence in 1970s enables spatial segregation of neuronal segments and detailed investigation that is otherwise limited with traditional culture methods. Although these compartmental chambers (e.g. Campenot chamber) have been proven valuable for the investigation of Peripheral Nervous System (PNS) neurons and to some extent within Central Nervous System (CNS) neurons, their utility has remained limited given the arduous manufacturing process, incompatibility with high-resolution optical imaging and limited throughput. The development in the area of microfabrication and microfluidics has enabled creation of next generation compartmentalized devices that are cheap, easy to manufacture, require reduced sample volumes, enable precise control over the cellular microenvironment both spatially as well as temporally, and permit highthroughput testing. In this review we briefly evaluate the various compartmentalization tools used for neurobiological research, and highlight application of the emerging microfluidic platforms towards in vitro single cell neurobiology. PMID:26813122

  14. COMPARTMENTAL MODEL OF NITRATE RETENTION IN STREAMS

    EPA Science Inventory

    A compartmental modeling approach is presented to route nitrate retention along a cascade of stream reach sections. A process transfer function is used for transient storage equations with first order reaction terms to represent nitrate uptake in the free stream, and denitrifica...

  15. Tracking Hazard Analysis Data in a Jungle of Changing Design

    SciTech Connect

    Sullivan, Robin S.; Young, Jonathan

    2006-05-14

    The biggest fear of the hazard analyst is the loss of data in the middle of the design jungle. When project schedules are demanding and design is changing rapidly it is essential that the hazard analysis data be tracked and kept current in order to provide the required project design, development, and regulatory support. Being able to identify the current information, as well as the past archived information, as the design progresses and to be able to show how the project is designing in safety through modifications based on hazard analysis results is imperative. At the DOE Hanford site in Washington State, Flour Hanford Inc is in the process of the removal and disposition of sludge from the 100 Area K Basins. The K Basins were used to store spent fuel from the operating reactors at the Hanford Site. The sludge is a by-product from the corrosion of the fuel and fuel storage canisters. The sludge removal project has been very dynamic involving the design, procurement and, more recently, the operation of processes at two basins, K East and K West. The project has an ambitious schedule with a large number of changes to design concepts. In order to support the complex K Basins project a technique to track the status of the hazard analysis data was developed. This paper will identify the most important elements of the tracking system and how it was used to assist the project in ensuring that current design data was reflected in a specific version of the hazard analysis and to show how the project was keeping up with the design and ensuring compliance with the requirements to design in safety. While the specifics of the data tracking strategy for the K Basins sludge removal project will be described in the paper, the general concepts of the strategy are applicable to similar projects requiring iteration of hazard analysis and design.

  16. The Garden and the Jungle: Burnett, Kipling and the Nature of Imperial Childhood

    ERIC Educational Resources Information Center

    Goodwin, Mary

    2011-01-01

    Imperial British India is the point of origin for protagonists in both Frances Hodgson Burnett's "The Secret Garden" (1911) and Rudyard Kipling's "The Jungle Books" (1894-1895), two influential children's stories in which late Victorian notions of childhood education and nature converge with those of national and imperial identity. In Burnett's…

  17. "Tales from the Brazilian Jungle": Antonio Rocha, Storyteller. Cue Sheet for Teachers.

    ERIC Educational Resources Information Center

    Rees, Elizabeth

    This performance guide is designed for teachers to use with students before and after a performance of "Tales from the Brazilian Jungle" with storyteller Antonio Rocha. The guide, called a "Cuesheet," contains four sheets for use in class. The first, "About the Performance," prepares students for understanding references to the Amazon rainforest,…

  18. Phase Separation: Linking Cellular Compartmentalization to Disease.

    PubMed

    Aguzzi, Adriano; Altmeyer, Matthias

    2016-07-01

    Eukaryotic cells are complex structures capable of coordinating numerous biochemical reactions in space and time. Key to such coordination is the subdivision of intracellular space into functional compartments. Compartmentalization can be achieved by intracellular membranes, which surround organelles and act as physical barriers. In addition, cells have developed sophisticated mechanisms to partition their inner substance in a tightly regulated manner. Recent studies provide compelling evidence that membraneless compartmentalization can be achieved by liquid demixing, a process culminating in liquid-liquid phase separation and the formation of phase boundaries. We discuss how this emerging concept may help in understanding dynamic reorganization of subcellular space and highlight its potential as a framework to explain pathological protein assembly in cancer and neurodegeneration. PMID:27051975

  19. Synthetic cells and organelles: compartmentalization strategies.

    PubMed

    Roodbeen, Renée; van Hest, Jan C M

    2009-12-01

    The recent development of RNA replicating protocells and capsules that enclose complex biosynthetic cascade reactions are encouraging signs that we are gradually getting better at mastering the complexity of biological systems. The road to truly cellular compartments is still very long, but concrete progress is being made. Compartmentalization is a crucial natural methodology to enable control over biological processes occurring within the living cell. In fact, compartmentalization has been considered by some theories to be instrumental in the creation of life. With the advancement of chemical biology, artificial compartments that can mimic the cell as a whole, or that can be regarded as cell organelles, have recently received much attention. The membrane between the inner and outer environment of the compartment has to meet specific requirements, such as semi-permeability, to allow communication and molecular transport over the border. The membrane can either be built from natural constituents or from synthetic polymers, introducing robustness to the capsule. PMID:19877005

  20. Compartmentalization of the deep cerebellar nuclei based on afferent projections and aldolase C expression.

    PubMed

    Sugihara, Izumi

    2011-09-01

    The distribution of aldolase C (zebrin II)-positive and -negative Purkinje cells (PCs) can be used to define about 20 longitudinally extended compartments in the cerebellar cortex of the rat, which may correspond to certain aspects of cerebellar functional localization. An equivalent compartmental organization may exist in the deep cerebellar nuclei (DCN). This DCN compartmentalization is primarily represented by the afferent projection pattern in the DCN. PC projections and collateral nuclear projections of olivocerebellar climbing fiber axons have a relatively localized terminal arbor in the DCN. Projections of these axons make a closed olivo-cortico-nuclear circuit to connect a longitudinal stripe-shaped cortical compartment to a small subarea in the DCN, which can be defined as a DCN compartment. The actual DCN compartmentalization, which has been revealed by systematically mapping these projections, is quite different from the cortical compartmentalization. The stripe-shaped alternation of aldolase C-positive and -negative narrow longitudinal compartments in the cerebellar cortex is transformed to the separate clustering of positive and negative compartments in the caudoventral and rostrodorsal DCN, respectively. The distinctive projection of aldolase C-positive and -negative PCs to the caudoventral and rostrodorsal DCN underlies this transformation. Accordingly, the medial cerebellar nucleus is divided into the rostrodorsal aldolase C-negative and caudoventral aldolase C-positive parts. The anterior and posterior interposed nuclei generally correspond to the aldolase C-negative and -positive parts, respectively. DCN compartmentalization is important for understanding functional localization in the DCN since it is speculated that aldolase C-positive and -negative compartments are generally associated with somatosensory and other functions, respectively. PMID:20981512

  1. Compartmentalization of the Edinburgh Human Metabolic Network

    PubMed Central

    2010-01-01

    Background Direct in vivo investigation of human metabolism is complicated by the distinct metabolic functions of various sub-cellular organelles. Diverse micro-environments in different organelles may lead to distinct functions of the same protein and the use of different enzymes for the same metabolic reaction. To better understand the complexity in the human metabolism, a compartmentalized human metabolic network with integrated sub-cellular location information is required. Results We extended the previously reconstructed Edinburgh Human Metabolic Network (EHMN) [Ma, et al. Molecular Systems Biology, 3:135, 2007] by integrating the sub-cellular location information for the reactions, adding transport reactions and refining the protein-reaction relationships based on the location information. Firstly, protein location information was obtained from Gene Ontology and complemented by a Swiss-Prot location keywords search. Then all the reactions in EHMN were assigned to a location based on the protein-reaction relationships to get a preliminary compartmentalized network. We investigated the localized sub-networks in each pathway to identify gaps and isolated reactions by connectivity analysis and refined the location information based on information from literature. As a result, location information for hundreds of reactions was revised and hundreds of incorrect protein-reaction relationships were corrected. Over 1400 transport reactions were added to link the location specific metabolic network. To validate the network, we have done pathway analysis to examine the capability of the network to synthesize or degrade certain key metabolites. Compared with a previously published human metabolic network (Human Recon 1), our network contains over 1000 more reactions assigned to clear cellular compartments. Conclusions By combining protein location information, network connectivity analysis and manual literature search, we have reconstructed a more complete

  2. Compartmentalized ATP synthesis in skeletal muscle triads.

    PubMed

    Han, J W; Thieleczek, R; Varsányi, M; Heilmeyer, L M

    1992-01-21

    Isolated skeletal muscle triads contain a compartmentalized glycolytic reaction sequence catalyzed by aldolase, triosephosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, and phosphoglycerate kinase. These enzymes express activity in the structure-associated state leading to synthesis of ATP in the triadic junction upon supply of glyceraldehyde 3-phosphate or fructose 1,6-bisphosphate. ATP formation occurs transiently and appears to be kinetically compartmentalized, i.e., the synthesized ATP is not in equilibrium with the bulk ATP. The apparent rate constants of the aldolase and the glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase reaction are significantly increased when fructose 1,6-bisphosphate instead of glyceraldehyde 3-phosphate is employed as substrate. The observations suggest that fructose 1,6-bisphosphate is especially effectively channelled into the junctional gap. The amplitude of the ATP transient is decreasing with increasing free [Ca2+] in the range of 1 nM to 30 microM. In the presence of fluoride, the ATP transient is significantly enhanced and its declining phase is substantially retarded. This observation suggests utilization of endogenously synthesized ATP in part by structure associated protein kinases and phosphatases which is confirmed by the detection of phosphorylated triadic proteins after gel electrophoresis and autoradiography. Endogenous protein kinases phosphorylate proteins of apparent Mr 450,000, 180,000, 160,000, 145,000, 135,000, 90,000, 54,000, 51,000, and 20,000, respectively. Some of these phosphorylated polypeptides are in the Mr range of known phosphoproteins involved in excitation-contraction coupling of skeletal muscle, which might give a first hint at the functional importance of the sequential glycolytic reactions compartmentalized in triads. PMID:1731894

  3. Ras trafficking, localization and compartmentalized signalling

    PubMed Central

    Prior, Ian A.; Hancock, John F.

    2012-01-01

    Ras proteins are proto-oncogenes that are frequently mutated in human cancers. Three closely related isoforms, HRAS, KRAS and NRAS, are expressed in all cells and have overlapping but distinctive functions. Recent work has revealed how differences between the Ras isoforms in their trafficking, localization and protein-membrane orientation enable signalling specificity to be determined. We review the various strategies used to characterize compartmentalized Ras localization and signalling. Localization is an important contextual modifier of signalling networks and insights from the Ras system are of widespread relevance for researchers interested in signalling initiated from membranes. PMID:21924373

  4. Passive Noise Filtering by Cellular Compartmentalization.

    PubMed

    Stoeger, Thomas; Battich, Nico; Pelkmans, Lucas

    2016-03-10

    Chemical reactions contain an inherent element of randomness, which presents itself as noise that interferes with cellular processes and communication. Here we discuss the ability of the spatial partitioning of molecular systems to filter and, thus, remove noise, while preserving regulated and predictable differences between single living cells. In contrast to active noise filtering by network motifs, cellular compartmentalization is highly effective and easily scales to numerous systems without requiring a substantial usage of cellular energy. We will use passive noise filtering by the eukaryotic cell nucleus as an example of how this increases predictability of transcriptional output, with possible implications for the evolution of complex multicellularity. PMID:26967282

  5. Fasciola hepatica Infection in an Indigenous Community of the Peruvian Jungle.

    PubMed

    Cabada, Miguel M; Castellanos-Gonzalez, Alejandro; Lopez, Martha; Caravedo, María Alejandra; Arque, Eulogia; White, Arthur Clinton

    2016-06-01

    Fasciola hepatica is a zoonotic infection with a worldwide distribution. Autochthonous cases have not been reported in the Amazon region of Peru. Operculated eggs resembling F. hepatica were identified in the stools of five out of 215 subjects in a remote indigenous community of the Peruvian jungle. Polymerase chain reaction targeting Fasciola hepatica cytochrome oxidase subunit 1 (COI) gene and sequencing of the products confirmed Fasciola infection. PMID:26976892

  6. Compartmental model of 18F-choline

    NASA Astrophysics Data System (ADS)

    Janzen, T.; Tavola, F.; Giussani, A.; Cantone, M. C.; Uusijärvi, H.; Mattsson, S.; Zankl, M.; Petoussi-Henß, N.; Hoeschen, C.

    2010-03-01

    The MADEIRA Project (Minimizing Activity and Dose with Enhanced Image quality by Radiopharmaceutical Administrations), aims to improve the efficacy and safety of 3D functional imaging by optimizing, among others, the knowledge of the temporal variation of the radiopharmaceuticals' uptake in and clearance from tumor and healthy tissues. With the help of compartmental modeling it is intended to optimize the time schedule for data collection and improve the evaluation of the organ doses to the patients. Administration of 18F-choline to screen for recurrence or the occurrence of metastases in prostate cancer patients is one of the diagnostic applications under consideration in the frame of the project. PET and CT images have been acquired up to four hours after injection of 18F-choline. Additionally blood and urine samples have been collected and measured in a gamma counter. The radioactivity concentration in different organs and data of plasma clearance and elimination into urine were used to set-up a compartmental model of the biokinetics of the radiopharmaceutical. It features a central compartment (blood) exchanging with organs. The structure describes explicitly liver, kidneys, spleen, plasma and bladder as separate units with a forcing function approach. The model is presented together with an evaluation of the individual and population kinetic parameters, and a revised time schedule for data collection is proposed. This optimized time schedule will be validated in a further set of patient studies.

  7. A mathematical analysis of second messenger compartmentalization

    NASA Astrophysics Data System (ADS)

    Chen, Wen; Levine, Herbert; Rappel, Wouter-Jan

    2008-12-01

    Intracellular compartmentalization of second messengers can lead to microdomains of elevated concentration that are thought to be involved in ensuring signaling specificity. Most experimental evidence for this compartmentalization involves the second messenger adenosine monophosphate (cAMP), which is degraded by phosphodiesterases (PDEs). One possible way of creating these compartments, supported by recent experiments, is to spatially separate the source of cAMP from regions of elevated PDE concentration. To quantify this possibility, we study here a simplified geometry in two dimensions (2D) and in three dimensions (3D), containing a cAMP point source and regions with different degradation constants. Using the symmetry of our geometry, we are able to derive steady state solutions for the cAMP concentration as a function of the system parameters. Furthermore, we show, using analytics as well as direct numerical simulations, that for physiologically relevant time scales the steady state solution has been reached. Our results indicate that elevating the degradation constant throughout the cell, except for a small microdomain surrounding the source, requires an unphysiologically high cellular PDE concentration. On the other hand, a tight spatial relationship of localized PDEs with the cAMP source can result in functional microdomains while maintaining a physiologically plausible cellular PDE concentration.

  8. Evidence for compartmentalization of mammalian carotenoid metabolism

    PubMed Central

    Palczewski, Grzegorz; Amengual, Jaume; Hoppel, Charles L.; von Lintig, Johannes

    2014-01-01

    The critical role of retinoids (vitamin A and its derivatives) for vision, reproduction, and survival has been well established. Vitamin A is produced from dietary carotenoids such as β-carotene by centric cleavage via the enzyme BCO1. The biochemical and molecular identification of a second structurally related β-carotene metabolizing enzyme, BCO2, has led to a prolonged debate about its relevance in vitamin A biology. While BCO1 cleaves provitamin A carotenoids, BCO2 is more promiscuous and also metabolizes nonprovitamin A carotenoids such as zeaxanthin into long-chain apo-carotenoids. Herein we demonstrate, in cell lines, that human BCO2 is associated with the inner mitochondrial membrane. Different human BCO2 isoforms possess cleavable N-terminal leader sequences critical for mitochondrial import. Subfractionation of murine hepatic mitochondria confirmed the localization of BCO2 to the inner mitochondrial membrane. Studies in BCO2-knockout mice revealed that zeaxanthin accumulates in the inner mitochondrial membrane; in contrast, β-carotene is retained predominantly in the cytoplasm. Thus, we provide evidence for a compartmentalization of carotenoid metabolism that prevents competition between BCO1 and BCO2 for the provitamin and the production of noncanonical β-carotene metabolites.—Palczewski, G., Amengual, J., Hoppel, C. L., von Lintig, J. Evidence for compartmentalization of mammalian carotenoid metabolism. PMID:25002123

  9. Compartmentation of Redox Metabolism in Malaria Parasites

    PubMed Central

    Rahlfs, Stefan; Przyborski, Jude M.; Becker, Katja

    2010-01-01

    Malaria, caused by the apicomplexan parasite Plasmodium, still represents a major threat to human health and welfare and leads to about one million human deaths annually. Plasmodium is a rapidly multiplying unicellular organism undergoing a complex developmental cycle in man and mosquito – a life style that requires rapid adaptation to various environments. In order to deal with high fluxes of reactive oxygen species and maintain redox regulatory processes and pathogenicity, Plasmodium depends upon an adequate redox balance. By systematically studying the subcellular localization of the major antioxidant and redox regulatory proteins, we obtained the first complete map of redox compartmentation in Plasmodium falciparum. We demonstrate the targeting of two plasmodial peroxiredoxins and a putative glyoxalase system to the apicoplast, a non-photosynthetic plastid. We furthermore obtained a complete picture of the compartmentation of thioredoxin- and glutaredoxin-like proteins. Notably, for the two major antioxidant redox-enzymes – glutathione reductase and thioredoxin reductase – Plasmodium makes use of alternative-translation-initiation (ATI) to achieve differential targeting. Dual localization of proteins effected by ATI is likely to occur also in other Apicomplexa and might open new avenues for therapeutic intervention. PMID:21203490

  10. Compartmentation of redox metabolism in malaria parasites.

    PubMed

    Kehr, Sebastian; Sturm, Nicole; Rahlfs, Stefan; Przyborski, Jude M; Becker, Katja

    2010-01-01

    Malaria, caused by the apicomplexan parasite Plasmodium, still represents a major threat to human health and welfare and leads to about one million human deaths annually. Plasmodium is a rapidly multiplying unicellular organism undergoing a complex developmental cycle in man and mosquito - a life style that requires rapid adaptation to various environments. In order to deal with high fluxes of reactive oxygen species and maintain redox regulatory processes and pathogenicity, Plasmodium depends upon an adequate redox balance. By systematically studying the subcellular localization of the major antioxidant and redox regulatory proteins, we obtained the first complete map of redox compartmentation in Plasmodium falciparum. We demonstrate the targeting of two plasmodial peroxiredoxins and a putative glyoxalase system to the apicoplast, a non-photosynthetic plastid. We furthermore obtained a complete picture of the compartmentation of thioredoxin- and glutaredoxin-like proteins. Notably, for the two major antioxidant redox-enzymes--glutathione reductase and thioredoxin reductase--Plasmodium makes use of alternative-translation-initiation (ATI) to achieve differential targeting. Dual localization of proteins effected by ATI is likely to occur also in other Apicomplexa and might open new avenues for therapeutic intervention. PMID:21203490

  11. Interplay of metagenomics and in vitro compartmentalization

    PubMed Central

    Ferrer, Manuel; Beloqui, Ana; Vieites, José María; Guazzaroni, María Eugenia; Berger, Ilana; Aharoni, Amir

    2009-01-01

    Summary In recent years, the application of approaches for harvesting DNA from the environment, the so‐called, ‘metagenomic approaches’ has proven to be highly successful for the identification, isolation and generation of novel enzymes. Functional screening for the desired catalytic activity is one of the key steps in mining metagenomic libraries, as it does not rely on sequence homology. In this mini‐review, we survey high‐throughput screening tools, originally developed for directed evolution experiments, which can be readily adapted for the screening of large libraries. In particular, we focus on the use of in vitro compartmentalization (IVC) approaches to address potential advantages and problems the merger of culture‐independent and IVC techniques might bring on the mining of enzyme activities in microbial communities. PMID:21261880

  12. Striatal cholinergic interneurons: birthdates predict compartmental localization.

    PubMed

    van Vulpen, E H; van der Kooy, D

    1998-07-01

    The striatal patch and matrix compartment neurons are born at different times during rat development. The majority of the early born neurons preferentially end up in the patch compartment, while the majority of the later born neurons end up in the matrix compartment. Although the cholinergic interneurons are all born early in neurogenesis (between embryonic day E12 and E17), and we would therefore expect them to be located mainly in the patches, they are relatively homogeneously distributed in the adult, with a preference for the matrix area just outside the patches (the intermediate zone). To ask if birthdate can predict the compartmental localization of cholinergic neurons in the striatum, we marked new postmitotic neurons in the embryo with a maternal injection of bromodeoxyuridine (BrdU) on E13, E15 or E17 and labeled the patch compartment with an injection of the retrograde tracer True Blue into the substantia nigra on postnatal day (P) 1. The pups were sacrificed at P40 and the tissue was processed for BrdU, choline acetyltransferase, and True Blue triple labeling. Cholinergic neurons that became postmitotic at E13, had a higher chance of ending up in the patch compartment compared to either the intermediate zone or the rest of the matrix compartment. On the other hand cholinergic neurons that became postmitotic at E17 had a higher chance of ending up in the matrix compartment (including the intermediate zone). We conclude that birthdate can predict compartmental localization, with the cholinergic neurons in the intermediate zone following the same pattern as the cholinergic neurons in the rest of the matrix compartment. Cholinergic neurons show the same relative birthdate/compartment relationship as do other striatal neurons, although the absolute birthdates of cholinergic neurons are shifted earlier in neurogenesis. PMID:9706390

  13. Field Testing of Compartmentalization Methods for Multifamily Construction

    SciTech Connect

    Ueno, K.; Lstiburek, J. W.

    2015-03-01

    The 2012 International Energy Conservation Code (IECC) has an airtightness requirement of 3 air changes per hour at 50 Pascals test pressure (3 ACH50) for single-family and multifamily construction (in climate zones 3–8). The Leadership in Energy & Environmental Design certification program and ASHRAE Standard 189 have comparable compartmentalization requirements. ASHRAE Standard 62.2 will soon be responsible for all multifamily ventilation requirements (low rise and high rise); it has an exceptionally stringent compartmentalization requirement. These code and program requirements are driving the need for easier and more effective methods of compartmentalization in multifamily buildings.

  14. Holocene cultural history of Red jungle fowl (Gallus gallus) and its domestic descendant in East Asia

    NASA Astrophysics Data System (ADS)

    Peters, Joris; Lebrasseur, Ophélie; Deng, Hui; Larson, Greger

    2016-06-01

    Nearly three decades ago, zooarchaeologists postulated that chicken husbandry was practiced in Northern China by ∼8.0 ka calBP. Recently, ancient mitogenome analyses of galliform remains suggested that Red jungle fowl (Gallus gallus) was already present in the Yellow River basin several millennia earlier, shortly after the onset of the Holocene. If these conclusions are correct, the origins of chicken domestication and husbandry in the region may have been spurred by agricultural innovations in the lower Yellow River basin including millet cultivation, pig husbandry, and dog breeding. In addition, the dispersal of poultry farming from East Asia to Asia Minor and Europe could therefore date to the Neolithic along ancient trade routes across Central Asia rather than via South Asia and Mesopotamia. For this scenario to be plausible, the post-Pleistocene climatic conditions must have been favourable to allow for a northward extension of the native distribution of tropical Red jungle fowl currently not found north of ∼25°N. This study combines Holocene palaeoclimate and archaeofaunal archives with new zooarchaeological insights alongside a discussion of methodological issues and cultural aspects in order to revisit the hypothesis of an early Holocene Gallus domestication and Neolithic poultry husbandry in Northern China. Our results regarding the natural and cultural history of Red jungle fowl and domestic chickens in East Asia, and the timing of chicken dispersal across the Old World suggest that an early Holocene domestication of chickens is problematic at best. We conclude by postulating an alternative model for the early exploitation of a key domestic species in present-day East Asia.

  15. Metabolic Flux and Compartmentation Analysis in the Brain In vivo

    PubMed Central

    Lanz, Bernard; Gruetter, Rolf; Duarte, João M. N.

    2013-01-01

    Through significant developments and progresses in the last two decades, in vivo localized nuclear magnetic resonance spectroscopy (MRS) became a method of choice to probe brain metabolic pathways in a non-invasive way. Beside the measurement of the total concentration of more than 20 metabolites, 1H MRS can be used to quantify the dynamics of substrate transport across the blood-brain barrier by varying the plasma substrate level. On the other hand, 13C MRS with the infusion of 13C-enriched substrates enables the characterization of brain oxidative metabolism and neurotransmission by incorporation of 13C in the different carbon positions of amino acid neurotransmitters. The quantitative determination of the biochemical reactions involved in these processes requires the use of appropriate metabolic models, whose level of details is strongly related to the amount of data accessible with in vivo MRS. In the present work, we present the different steps involved in the elaboration of a mathematical model of a given brain metabolic process and its application to the experimental data in order to extract quantitative brain metabolic rates. We review the recent advances in the localized measurement of brain glucose transport and compartmentalized brain energy metabolism, and how these reveal mechanistic details on glial support to glutamatergic and GABAergic neurons. PMID:24194729

  16. Compartmental model of leucine kinetics in humans.

    PubMed

    Cobelli, C; Saccomani, M P; Tessari, P; Biolo, G; Luzi, L; Matthews, D E

    1991-10-01

    The complexity of amino acid and protein metabolism has limited the development of comprehensive, accurate whole body kinetic models. For leucine, simplified approaches are in use to measure in vivo leucine fluxes, but their domain of validity is uncertain. We propose here a comprehensive compartmental model of the kinetics of leucine and alpha-ketoisocaproate (KIC) in humans. Data from a multiple-tracer administration were generated with a two-stage (I and II) experiment. Six normal subjects were studied. In experiment I, labeled leucine and KIC were simultaneously injected into plasma. Four plasma leucine and KIC tracer concentration curves and label in the expired CO2 were measured. In experiment II, labeled bicarbonate was injected into plasma, and labeled CO2 in the expired air was measured. Radioactive (L-[1-14C]leucine, [4,5-3H]KIC, [14C]bicarbonate) and stable isotope (L-[1-13C]leucine, [5,5,5-2H3]KIC, [13C]bicarbonate) tracers were employed. The input format was a bolus (impulse) dose in the radioactive case and a constant infusion in the stable isotope case. A number of physiologically based, linear time-invariant compartmental models were proposed and tested against the data. The model finally chosen for leucine-KIC kinetics has 10 compartments: 4 for leucine, 3 for KIC, and 3 for bicarbonate. The model is a priori uniquely identifiable, and its parameters were estimated with precision from the five curves of experiment I. The separate assessment of bicarbonate kinetics (experiment II) was shown to be unnecessary. The model defines masses and fluxes of leucine in the organism, in particular its intracellular appearance from protein breakdown, its oxidation, and its incorporation into proteins. An important feature of the model is its ability to estimate leucine oxidation by resolving the bicarbonate model in each individual subject. Finally, the model allows the assessment of the domain of validity of the simpler commonly used models. PMID:1928344

  17. From rum jungle to Wismut-reducing the environmental impact of uranium mining and milling

    SciTech Connect

    Zuk, W.M.; Jeffree, R.A.; Levins, D.M.

    1994-12-31

    Australia has a long history of uranium mining. In the early days, little attention was given to environmental matters and considerable pollution occurred. Ansto has been involved in rehabilitation of a number of the early uranium mining sites, from Rum Jungle in Australia`s Northern Territory to Wismut in Germany, and is working with current producers to minimise the environmental impact of their operations. Ansto`s expertise is extensive and includes, inter alia, amelioration of acid mine drainage, radon measurement and control, treatment of mill wastes, management of tailings, monitoring of seepage plumes, mathematical modelling of pollutant transport and biological impacts in a tropical environment.

  18. Digital processing of satellite imagery application to jungle areas of Peru

    NASA Technical Reports Server (NTRS)

    Pomalaza, J. C. (Principal Investigator); Pomalaza, C. A.; Espinoza, J.

    1976-01-01

    The author has identified the following significant results. The use of clustering methods permits the development of relatively fast classification algorithms that could be implemented in an inexpensive computer system with limited amount of memory. Analysis of CCTs using these techniques can provide a great deal of detail permitting the use of the maximum resolution of LANDSAT imagery. Potential cases were detected in which the use of other techniques for classification using a Gaussian approximation for the distribution functions can be used with advantage. For jungle areas, channels 5 and 7 can provide enough information to delineate drainage patterns, swamp and wet areas, and make a reasonable broad classification of forest types.

  19. Subcellular compartmentation of ascorbate and its variation in disease states.

    PubMed

    Bánhegyi, Gábor; Benedetti, Angelo; Margittai, Eva; Marcolongo, Paola; Fulceri, Rosella; Németh, Csilla E; Szarka, András

    2014-09-01

    Beyond its general role as antioxidant, specific functions of ascorbate are compartmentalized within the eukaryotic cell. The list of organelle-specific functions of ascorbate has been recently expanded with the epigenetic role exerted as a cofactor for DNA and histone demethylases in the nucleus. Compartmentation necessitates the transport through intracellular membranes; members of the GLUT family and sodium-vitamin C cotransporters mediate the permeation of dehydroascorbic acid and ascorbate, respectively. Recent observations show that increased consumption and/or hindered entrance of ascorbate in/to a compartment results in pathological alterations partially resembling to scurvy, thus diseases of ascorbate compartmentation can exist. The review focuses on the reactions and transporters that can modulate ascorbate concentration and redox state in three compartments: endoplasmic reticulum, mitochondria and nucleus. By introducing the relevant experimental and clinical findings we make an attempt to coin the term of ascorbate compartmentation disease. PMID:24907663

  20. Compartmentalization of Immune Responses in Human Tuberculosis

    PubMed Central

    Rahman, Sayma; Gudetta, Berhanu; Fink, Joshua; Granath, Anna; Ashenafi, Senait; Aseffa, Abraham; Derbew, Milliard; Svensson, Mattias; Andersson, Jan; Brighenti, Susanna Grundström

    2009-01-01

    Immune responses were assessed at the single-cell level in lymph nodes from children with tuberculous lymphadenitis. Tuberculosis infection was associated with tissue remodeling of lymph nodes as well as altered cellular composition. Granulomas were significantly enriched with CD68+ macrophages expressing the M. tuberculosis complex-specific protein antigen MPT64 and inducible nitric oxide synthase. There was a significant increase in CD8+ cytolytic T cells surrounding the granuloma; however, CD8+ T cells expressed low levels of the cytolytic and antimicrobial effector molecules perforin and granulysin in the granulomatous lesions. Quantitative real-time mRNA analysis revealed that interferon-γ, tumor necrosis factor-α, and interleukin-17 were not up-regulated in infected lymph nodes, but there was a significant induction of both transforming growth factor-β and interleukin-13. In addition, granulomas contained an increased number of CD4+FoxP3+ T cells co-expressing the immunoregulatory cytotoxic T-lymphocyte antigen-4 and glucocorticoid-induced tumor necrosis factor receptor molecules. Low numbers of CD8+ T cells in the lesions correlated with high levels of transforming growth factor-β and FoxP3+ regulatory T cells, suggesting active immunosuppression at the local infection site. Compartmentalization and skewing of the immune response toward a regulatory phenotype may result in an uncoordinated effector T-cell response that reduces granule-mediated killing of M. tuberculosis-infected cells and subsequent disease control. PMID:19435796

  1. Compartmentalized Cytokine Responses in Hidradenitis Suppurativa

    PubMed Central

    Savva, Athina; Kersten, Brigit; Pistiki, Aikaterini; van de Veerdonk, Frank L.; Netea, Mihai G.; van der Meer, Jos W.; Giamarellos-Bourboulis, Evangelos J.

    2015-01-01

    Background Favorable treatment outcomes with TNF blockade led us to explore cytokine responses in hidradenitis suppurativa (HS). Methods Blood monocytes of 120 patients and 24 healthy volunteers were subtyped by flow cytometry. Isolated blood mononuclear cells (PBMCs) were stimulated for cytokine production; this was repeated in 13 severe patients during treatment with etanercept. Cytokines in pus were measured. Results CD14brightCD16dim inflammatory monocytes and patrolling monocytes were increased in Hurley III patients. Cytokine production by stimulated PBMCs was low compared to controls but the cytokine gene copies did not differ, indicating post-translational inhibition. The low production of IL-17 was restored, when cells were incubated with adalimumab. In pus, high concentrations of pro-inflammatory cytokines were detected. Based on the patterns, six different cytokine profiles were discerned, which are potentially relevant for the choice of treatment. Clinical improvement with etanercept was predicted by increased production of IL-1β and IL-17 by PBMCs at week 8. Conclusions Findings indicate compartmentalized cytokine expression in HS; high in pus but suppressed in PBMCs. This is modulated through blockade of TNF. PMID:26091259

  2. Compartmentalized Innervation of Primate Lateral Rectus Muscle

    PubMed Central

    Peng, Michelle; Poukens, Vadims; da Silva Costa, Roberta Martins; Yoo, Lawrence; Tychsen, Lawrence

    2010-01-01

    Purpose. Skeletal and craniofacial muscles are frequently composed of multiple neuromuscular compartments that serve different physiological functions. Evidence of possible regional selectivity in LR intramuscular innervation was sought in a study of the anatomic potential of lateral rectus (LR) muscle compartmentalization. Methods. Whole orbits of two humans and five macaque monkeys were serially sectioned at 10-μm thickness and stained with Masson trichrome. The abducens nerve (CN6) was traced anteriorly from the deep orbit as it branched to enter the LR and arborized among extraocular muscle (EOM) fibers. Three-dimensional reconstruction was performed in human and monkey orbits. Results. Findings were in concordance in the monkey and human orbits. External to the LR global surface, CN6 bifurcated into approximately equal-sized trunks before entering the global layer. Subsequent arborization showed a systematic topography, entering a well-defined inferior zone 0.4 to 2.5 mm more posteriorly than branches entering the largely nonoverlapping superior zone. Zonal innervation remained segregated anteriorly and laterally within the LR. Conclusions. Consistent segregation of intramuscular CN6 arborization in humans and monkeys suggests functionally distinct superior and inferior zones for the LR. Since the LR is shaped as a broad vertical strap, segregated control of the two zones could activate them separately, potentially mediating previously unappreciated but substantial torsional and vertical oculorotary LR actions. PMID:20435590

  3. Compartmentalization and Transport in Synthetic Vesicles.

    PubMed

    Schmitt, Christine; Lippert, Anna H; Bonakdar, Navid; Sandoghdar, Vahid; Voll, Lars M

    2016-01-01

    Nanoscale vesicles have become a popular tool in life sciences. Besides liposomes that are generated from phospholipids of natural origin, polymersomes fabricated of synthetic block copolymers enjoy increasing popularity, as they represent more versatile membrane building blocks that can be selected based on their specific physicochemical properties, such as permeability, stability, or chemical reactivity. In this review, we focus on the application of simple and nested artificial vesicles in synthetic biology. First, we provide an introduction into the utilization of multicompartmented vesosomes as compartmentalized nanoscale bioreactors. In the bottom-up development of protocells from vesicular nanoreactors, the specific exchange of pathway intermediates across compartment boundaries represents a bottleneck for future studies. To date, most compartmented bioreactors rely on unspecific exchange of substrates and products. This is either based on changes in permeability of the coblock polymer shell by physicochemical triggers or by the incorporation of unspecific porin proteins into the vesicle membrane. Since the incorporation of membrane transport proteins into simple and nested artificial vesicles offers the potential for specific exchange of substances between subcompartments, it opens new vistas in the design of protocells. Therefore, we devote the main part of the review to summarize the technical advances in the use of phospholipids and block copolymers for the reconstitution of membrane proteins. PMID:26973834

  4. Compartmentalization and Transport in Synthetic Vesicles

    PubMed Central

    Schmitt, Christine; Lippert, Anna H.; Bonakdar, Navid; Sandoghdar, Vahid; Voll, Lars M.

    2016-01-01

    Nanoscale vesicles have become a popular tool in life sciences. Besides liposomes that are generated from phospholipids of natural origin, polymersomes fabricated of synthetic block copolymers enjoy increasing popularity, as they represent more versatile membrane building blocks that can be selected based on their specific physicochemical properties, such as permeability, stability, or chemical reactivity. In this review, we focus on the application of simple and nested artificial vesicles in synthetic biology. First, we provide an introduction into the utilization of multicompartmented vesosomes as compartmentalized nanoscale bioreactors. In the bottom-up development of protocells from vesicular nanoreactors, the specific exchange of pathway intermediates across compartment boundaries represents a bottleneck for future studies. To date, most compartmented bioreactors rely on unspecific exchange of substrates and products. This is either based on changes in permeability of the coblock polymer shell by physicochemical triggers or by the incorporation of unspecific porin proteins into the vesicle membrane. Since the incorporation of membrane transport proteins into simple and nested artificial vesicles offers the potential for specific exchange of substances between subcompartments, it opens new vistas in the design of protocells. Therefore, we devote the main part of the review to summarize the technical advances in the use of phospholipids and block copolymers for the reconstitution of membrane proteins. PMID:26973834

  5. Case Report: Cutaneous Leishmaniasis in Cuban Immigrants to Texas who Traveled through the Darién Jungle, Panama

    PubMed Central

    Barry, Meagan A.; Koshelev, Misha V.; Sun, Grace S.; Grekin, Sarah J.; Stager, Charles E.; Diwan, A. Hafeez; Wasko, Carina A.; Murray, Kristy O.; Woc-Colburn, Laila

    2014-01-01

    Cutaneous leishmaniasis is rarely seen in the United States. Four Cuban immigrants traveled along the same route at different times from Cuba to Ecuador, then northward, including through the Darién Jungle in Panama. These patients had chronic ulcerative non-healing skin lesions and were given a diagnosis of leishmaniasis. PMID:24865687

  6. Blind estimation of compartmental model parameters.

    PubMed

    Di Bella, E V; Clackdoyle, R; Gullberg, G T

    1999-03-01

    Computation of physiologically relevant kinetic parameters from dynamic PET or SPECT imaging requires knowledge of the blood input function. This work is concerned with developing methods to accurately estimate these kinetic parameters blindly; that is, without use of a directly measured blood input function. Instead, only measurements of the output functions--the tissue time-activity curves--are used. The blind estimation method employed here minimizes a set of cross-relation equations, from which the blood term has been factored out, to determine compartmental model parameters. The method was tested with simulated data appropriate for dynamic SPECT cardiac perfusion imaging with 99mTc-teboroxime and for dynamic PET cerebral blood flow imaging with 15O water. The simulations did not model the tomographic process. Noise levels typical of the respective modalities were employed. From three to eight different regions were simulated, each with different time-activity curves. The time-activity curve (24 or 70 time points) for each region was simulated with a compartment model. The simulation used a biexponential blood input function and washin rates between 0.2 and 1.3 min(-1) and washout rates between 0.2 and 1.0 min(-1). The system of equations was solved numerically and included constraints to bound the range of possible solutions. From the cardiac simulations, washin was determined to within a scale factor of the true washin parameters with less than 6% bias and 12% variability. 99mTc-teboroxime washout results had less than 5% bias, but variability ranged from 14% to 43%. The cerebral blood flow washin parameters were determined with less than 5% bias and 4% variability. The washout parameters were determined with less than 4% bias, but had 15-30% variability. Since washin is often the parameter of most use in clinical studies, the blind estimation approach may eliminate the current necessity of measuring the input function when performing certain dynamic studies

  7. Towards repurposing the yeast peroxisome for compartmentalizing heterologous metabolic pathways

    DOE PAGESBeta

    DeLoache, William C.; Russ, Zachary N.; Dueber, John E.

    2016-03-30

    Compartmentalization of enzymes into organelles is a promising strategy for limiting metabolic crosstalk and improving pathway efficiency, but improved tools and design rules are needed to make this strategy available to more engineered pathways. Here we focus on the Saccharomyces cerevisiae peroxisome and develop a sensitive high-throughput assay for peroxisomal cargo import. We identify an enhanced peroxisomal targeting signal type 1 (PTS1) for rapidly sequestering non-native cargo proteins. Additionally, we perform the first systematic in vivo measurements of nonspecific metabolite permeability across the peroxisomal membrane using a polymer exclusion assay. Finally, we apply these new insights to compartmentalize a two-enzymemore » pathway in the peroxisome and characterize the expression regimes where compartmentalization leads to improved product titre. Lastly, this work builds a foundation for using the peroxisome as a synthetic organelle, highlighting both promise and future challenges on the way to realizing this goal.« less

  8. Evidence of recent jungle yellow-fever activity in eastern Panama*

    PubMed Central

    Galindo, Pedro; Srihongse, Sunthorn

    1967-01-01

    Outbreaks of jungle yellow fever in man have been recorded twice from eastern Panama of recent years, first in 1948 and again in 1956. Since then, a close surveillance has been maintained on virus activity in eastern Panama. Recent field observations and serological tests on 402 monkey sera indicate that there was an outbreak of yellow fever among monkeys of southern Darién Province some time between 1963 and 1965. It does not appear that the outbreak has spread as yet to other areas. Virus transmission may have been permanently disrupted during the drought which affected the region in 1965. However, if the virus had managed to survive this unfavourable period, an epizootic wave might have evolved, invading forested areas immediately east of the Panama Canal, now inhabited by a dense non-immune human population. PMID:4962725

  9. Modeling the Kinetics of a Memory-Associated Immediate Early Gene's Compartmental Expression After Sensory Experience

    NASA Astrophysics Data System (ADS)

    Willats, Adam; Ivanova, Tamara; Prinz, Astrid; Liu, Robert

    2015-03-01

    Immediate Early Genes (IEGs) are rapidly and transiently transcribed in neurons after a sensory experience. Some of these genes act as effector IEGs, which mediate specific effects on cellular function. Arc is one such effector IEG that is essential for synaptic plasticity and memory consolidation in hippocampus and cortex. The expression of Arc in neurons has previously been examined using an imaging method known as Compartmental Analysis of Temporal Fluorescent In-Situ Hybridization. Previous work found that the time course of Arc expression within the nuclear and perinuclear cytoplasmic compartments of a neuron is altered by prior sensory experience. We explore a simple model of the kinetics of IEG transcription and nuclear export, with the aim of eventually uncovering possible mechanisms for how experience alters expression kinetics. Thus far, we characterize our compartmental model using phase-plane analysis and validate it against several IEG expression data sets, including one where prior experience with vocalizing mice alters the time course of call-induced Arc expression in the auditory cortex of a listening mouse. Our model provides a framework to explore why Arc expression may change depending on a receiver's past sound experience and internal state. Adam Willats was supported by NIH Training Grant 5T90DA032466. This research was also supported by NIDCD R01 DC8343.

  10. Subcellular compartmentalization of docking protein-1 contributes to progression in colorectal cancer.

    PubMed

    Friedrich, Teresa; Söhn, Michaela; Gutting, Tobias; Janssen, Klaus-Peter; Behrens, Hans-Michael; Röcken, Christoph; Ebert, Matthias P A; Burgermeister, Elke

    2016-06-01

    Full-length (FL) docking protein-1 (DOK1) is an adapter protein which inhibits growth factor and immune response pathways in normal tissues, but is frequently lost in human cancers. Small DOK1 variants remain in cells of solid tumors and leukemias, albeit, their functions are elusive. To assess the so far unknown role of DOK1 in colorectal cancer (CRC), we generated DOK1 mutants which mimic the domain structure and subcellular distribution of DOK1 protein variants in leukemia patients. We found that cytoplasmic DOK1 activated peroxisome-proliferator-activated-receptor-gamma (PPARγ) resulting in inhibition of the c-FOS promoter and cell proliferation, whereas nuclear DOK1 was inactive. PPARγ-agonist increased expression of endogenous DOK1 and interaction with PPARγ. Forward translation of this cell-based signaling model predicted compartmentalization of DOK1 in patients. In a large series of CRC patients, loss of DOK1 protein was associated with poor prognosis at early tumor stages (*p=0.001; n=1492). In tumors with cytoplasmic expression of DOK1, survival was improved, whereas nuclear localization of DOK1 correlated with poor outcome, indicating that compartmentalization of DOK1 is critical for CRC progression. Thus, DOK1 was identified as a prognostic factor for non-metastatic CRC, and, via its drugability by PPARγ-agonist, may constitute a potential target for future cancer treatments. PMID:27428427

  11. Subcelluar compartmentalization of cAMP-dependent protein kinase regulatory subunits during palate ontogeny

    SciTech Connect

    Linask, K.K.; Greene, R.M. )

    1989-01-01

    Mammalian palatal ontogeny involves epithelial-mesenchymal interactions, cell differentiation, and cell movement. These events occur on days 12, 13, and 14 of gestation in the C57BL/6J mouse embryo. During this period intracellular cAMP levels and cAMP-dependent protein kinase (cAMP-dPK) levels in the palate transiently elevate. Cyclic AMP activates cAMP-dPK by binding primarily to two types of regulatory subunits of this enzyme, designated as R{sub I} and R{sub II}. To assess whether differential compartmentalization of the regulatory subunits occurs during palatal ontogeny, cytosolic, nuclear, and particulate fractions were prepared from day 12, 13, and 14 embryonic maxillary and palatal tissue. After photo-affinity labeling of each fraction with 8-azido ({sup 32}P) cAMP, SDS-PAGE, and autoradiography, autoradiograms were analyzed densitometrically. The R{sub I} isoform predominated in the nuclear and particulate fractions on all three developmental days; whereas R{sub II} predominated in the cytosolic fractions. Thus, differential compartmentalization of cAMP-dPK may be a means by which cAMP dependent responses are regulated during palatogenesis.

  12. Continuing pollution from the Rum Jungle U-Cu project: a critical evaluation of environmental monitoring and rehabilitation.

    PubMed

    Mudd, Gavin M; Patterson, James

    2010-05-01

    The former Rum Jungle uranium-copper project, Australia, is an internationally important case study on environmental pollution from and rehabilitation of mining. The Rum Jungle mining project is briefly reviewed, followed by a critical evaluation of monitoring data and pollution loads prior to and after rehabilitation - leading to the conclusion that rehabilitation has clearly failed the test of time after just two decades. The most critical findings are the need to understand pollution cycles holistically, and designing monitoring regimes to match, explicit inclusion of radiological criteria (lacking in original planning), and finally the need to set targets based on environmental criteria. Two examples include polluted groundwater which was excluded from rehabilitation and the poor design, construction and/or performance of engineered soil covers - both leading to increasing acid drainage impacts on the Finniss River. The critical review therefore presents a valuable case study of the environmental performance of uranium mine site rehabilitation. PMID:20176422

  13. The challenges of cellular compartmentalization in plant metabolic engineering.

    PubMed

    Heinig, Uwe; Gutensohn, Michael; Dudareva, Natalia; Aharoni, Asaph

    2013-04-01

    The complex metabolic networks in plants are highly compartmentalized and biochemical steps of a single pathway can take place in multiple subcellular locations. Our knowledge regarding reactions and precursor compounds in the various cellular compartments has increased in recent years due to innovations in tracking the spatial distribution of proteins and metabolites. Nevertheless, to date only few studies have integrated subcellular localization criteria in metabolic engineering attempts. Here, we highlight the crucial factors for subcellular-localization-based strategies in plant metabolic engineering including substrate availability, enzyme targeting, the role of transporters, and multigene transfer approaches. The availability of compartmentalized metabolic network models for plants in the near future will greatly advance the integration of localization constraints in metabolic engineering experiments and aid in predicting their outcomes. PMID:23246154

  14. Ultrastructural and histochemical properties of the olfactory system in the japanese jungle crow, Corvus macrorhynchos.

    PubMed

    Kondoh, Daisuke; Nashimoto, Mai; Kanayama, Shunsaku; Nakamuta, Nobuaki; Taniguchi, Kazuyuki

    2011-08-01

    Although it has been commonly believed that birds are more dependent on the vision and audition than the olfaction, recent studies indicate that the olfaction of birds is related to the reproductive, homing, and predatory behaviors. In an attempt to reveal the dependence on the olfactory system in crows, we examined the olfactory system of the Japanese jungle crow (Corvus macrorhynchos) by histological, ultrastructural, and lectin histochemical methods. The olfactory epithelium (OE) of the crow occupied remarkably a small area of the nasal cavity (NC) and had the histological and ultrastructural features like other birds. The olfactory bulb (OB) of the crow was remarkably small and did not possess the olfactory ventricle. The left and right halves of the OB were fused in many cases. In the lectin histochemistry, soybean agglutinin (SBA) and Vicia villosa agglutinin (VVA) stained a small number of the receptor cells (RCs) in the OE and the olfactory nerve layer (ONL) and glomerular layer (GL) on the dorsocaudal region of the OB. Phaseolus vulgaris agglutinin-E (PHA-E) stained several RCs in the OE and the ONL and GL on the ventral region of the OB. These results suggest that 1) the crow has less-developed olfactory system than other birds, and 2) the dedicated olfactory receptor cells project their axons to the specific regions of the OB in the crow. PMID:21478653

  15. Quasi-steady state reduction for compartmental systems

    NASA Astrophysics Data System (ADS)

    Goeke, Alexandra; Lax, Christian

    2016-07-01

    We present a method to determine an asymptotic reduction (in the sense of Tikhonov and Fenichel) for singularly perturbed compartmental systems in the presence of slow transport. It turns out that the reduction can be derived from the individual interaction terms alone. We apply the result to spatially discretized reaction-diffusion systems and obtain (based on the reduced discretized systems) a heuristic to reduce reaction-diffusion systems in presence of slow diffusion.

  16. Fractional two-compartmental model for articaine serum levels

    NASA Astrophysics Data System (ADS)

    Petronijevic, Branislava; Sarcev, Ivan; Zorica, Dusan; Janev, Marko; Atanackovic, Teodor M.

    2016-06-01

    Two fractional two-compartmental models are applied to the pharmacokinetics of articaine. Integer order derivatives are replaced by fractional derivatives, either of different, or of same orders. Models are formulated so that the mass balance is preserved. Explicit forms of the solutions are obtained in terms of the Mittag-Leffler functions. Pharmacokinetic parameters are determined by the use of the evolutionary algorithm and trust regions optimization to recover the experimental data.

  17. Differential Lateral Rectus Compartmental Contraction during Ocular Counter-Rolling

    PubMed Central

    Clark, Robert A.; Demer, Joseph L.

    2012-01-01

    Purpose. The lateral rectus (LR) and medial rectus (MR) extraocular muscles (EOMs) have largely nonoverlapping superior and inferior innervation territories, suggesting functional compartmental specialization. We used magnetic resonance imaging (MRI) in humans to investigate differential compartmental activity in the rectus EOMs during head tilt, which evokes ocular counter-rolling, a torsional vestibulo-ocular reflex (VOR). Methods. MRI in quasi-coronal planes was analyzed during target-controlled central gaze in 90° right and left head tilts in 12 normal adults. Cross sections and posterior partial volumes of the transverse portions of the four rectus EOMs were compared in contiguous image planes 2 mm thick spanning the orbit from origins to globe equator, and used as indicators of contractility. Results. Horizontal rectus EOMs had significantly greater posterior volumes and maximum cross sections in their inferior compartments (P < 10−8). In orbit tilt up (extorted) compared with orbit tilt down (intorted) head tilts, contractile changes in LR maximum cross section (P < 0.0001) and posterior partial volume (P < 0.05) were significantly greater in the inferior but not in the superior compartment. These changes were not explainable by horizontal or vertical eye position changes. A weaker compartmental effect was suggested for MR. The vertical rectus EOMs did not exhibit significant compartmental contractile changes during head tilt. Mechanical modeling suggests that differential LR contraction may contribute to physiological cyclovertical effects. Conclusions. Selective activation of the two LR, and possibly MR, compartments correlates with newly recognized segregation of intramuscular innervation into distinct compartments, and probably contributes to noncommutative torsion during the VOR. PMID:22427572

  18. Accelerating compartmental modeling on a graphical processing unit.

    PubMed

    Ben-Shalom, Roy; Liberman, Gilad; Korngreen, Alon

    2013-01-01

    Compartmental modeling is a widely used tool in neurophysiology but the detail and scope of such models is frequently limited by lack of computational resources. Here we implement compartmental modeling on low cost Graphical Processing Units (GPUs), which significantly increases simulation speed compared to NEURON. Testing two methods for solving the current diffusion equation system revealed which method is more useful for specific neuron morphologies. Regions of applicability were investigated using a range of simulations from a single membrane potential trace simulated in a simple fork morphology to multiple traces on multiple realistic cells. A runtime peak 150-fold faster than the CPU was achieved. This application can be used for statistical analysis and data fitting optimizations of compartmental models and may be used for simultaneously simulating large populations of neurons. Since GPUs are forging ahead and proving to be more cost-effective than CPUs, this may significantly decrease the cost of computation power and open new computational possibilities for laboratories with limited budgets. PMID:23508232

  19. Cross-membranes orchestrate compartmentalization and morphogenesis in Streptomyces

    PubMed Central

    Celler, Katherine; Koning, Roman I.; Willemse, Joost; Koster, Abraham J.; van Wezel, Gilles P.

    2016-01-01

    Far from being simple unicellular entities, bacteria have complex social behaviour and organization, living in large populations, and some even as coherent, multicellular entities. The filamentous streptomycetes epitomize such multicellularity, growing as a syncytial mycelium with physiologically distinct hyphal compartments separated by infrequent cross-walls. The viability of mutants devoid of cell division, which can be propagated from fragments, suggests the presence of a different form of compartmentalization in the mycelium. Here we show that complex membranes, visualized by cryo-correlative light microscopy and electron tomography, fulfil this role. Membranes form small assemblies between the cell wall and cytoplasmic membrane, or, as evidenced by FRAP experiments, large protein-impermeable cross-membrane structures, which compartmentalize the multinucleoid mycelium. All areas containing cross-membrane structures are nucleoid-restricted zones, suggesting that the membrane assemblies may also act to protect nucleoids from cell-wall restructuring events. Our work reveals a novel mechanism of controlling compartmentalization and development in multicellular bacteria. PMID:27291257

  20. Sodium Transport and Compartmentation in Spergularia marina1

    PubMed Central

    Lazof, Dennis; Cheeseman, John M.

    1986-01-01

    In this paper, a combination of tracer uptake, efflux, and pulse-chase techniques is applied to the problem of compartmentation of Na+ (24Na+) in the roots of intact, midvegetative Spergularia marina (L.) Griseb. plants. An approach is presented for conducting useful compartmental analysis when it is known that the assumptions required for straightforward interpretations of influx and efflux studies are invalid. Linear rates of 24Na+ accumulation in both roots and shoots were attained within at most a few minutes following the start of labeling. Shoot 24Na+ contents equaled root contents within about 20 minutes. Analysis of root accumulation rates, and compartmental and pulse-chase efflux studies indicated that the unidirectional flux rates involved were at least an order of magnitude greater than linear rates of root and shoot accumulation. These rapid fluxes involved only a small portion of the total root Na+ (about 1%). The results suggest the existence of a small symplastic compartment, distinct from the `bulk cytoplasm,' rapidly exchanging with the medium, and responsible for delivery of Na+ to the xylem. The physical identity of this compartment and its physiological significance are discussed with respect to precedents in the literature. PMID:16664895

  1. Compartmentalized Droplets for Continuous Flow Liquid-Liquid Interface Catalysis.

    PubMed

    Zhang, Ming; Wei, Lijuan; Chen, Huan; Du, Zhiping; Binks, Bernard P; Yang, Hengquan

    2016-08-17

    To address the limitations of batch organic-aqueous biphasic catalysis, we develop a conceptually novel method termed Flow Pickering Emulsion, or FPE, to process biphasic reactions in a continuous flow fashion. This method involves the compartmentalization of bulk water into micron-sized droplets based on a water-in-oil Pickering emulsion, which are packed into a column reactor. The compartmentalized water droplets can confine water-soluble catalysts, thus "immobilizing" the catalyst in the column reactor, while the interstices between the droplets allow the organic (oil) phase to flow. Key fundamental principles underpinning this method such as the oil phase flow behavior, the stability of compartmentalized droplets and the confinement capability of these droplets toward water-soluble catalysts are experimentally and theoretically investigated. As a proof of this concept, case studies including a sulfuric acid-catalyzed addition reaction, a heteropolyacid-catalyzed ring opening reaction and an enzyme-catalyzed chiral reaction demonstrate the generality and versatility of the FPE method. Impressively, in addition to the excellent durability, the developed FPE reactions exhibit up to 10-fold reaction efficiency enhancement in comparison to the existing batch reactions, indicating a unique flow interface catalysis effect. This study opens up a new avenue to allow conventional biphasic catalysis reactions to access more sustainable and efficient flow chemistry using an innovative liquid-liquid interface protocol. PMID:27429173

  2. Cross-membranes orchestrate compartmentalization and morphogenesis in Streptomyces.

    PubMed

    Celler, Katherine; Koning, Roman I; Willemse, Joost; Koster, Abraham J; van Wezel, Gilles P

    2016-01-01

    Far from being simple unicellular entities, bacteria have complex social behaviour and organization, living in large populations, and some even as coherent, multicellular entities. The filamentous streptomycetes epitomize such multicellularity, growing as a syncytial mycelium with physiologically distinct hyphal compartments separated by infrequent cross-walls. The viability of mutants devoid of cell division, which can be propagated from fragments, suggests the presence of a different form of compartmentalization in the mycelium. Here we show that complex membranes, visualized by cryo-correlative light microscopy and electron tomography, fulfil this role. Membranes form small assemblies between the cell wall and cytoplasmic membrane, or, as evidenced by FRAP experiments, large protein-impermeable cross-membrane structures, which compartmentalize the multinucleoid mycelium. All areas containing cross-membrane structures are nucleoid-restricted zones, suggesting that the membrane assemblies may also act to protect nucleoids from cell-wall restructuring events. Our work reveals a novel mechanism of controlling compartmentalization and development in multicellular bacteria. PMID:27291257

  3. Field Testing of Compartmentalization Methods for Multifamily Construction

    SciTech Connect

    Ueno, K.; Lstiburek, J.

    2015-03-01

    The 2012 IECC has an airtightness requirement of 3 air changes per hour at 50 Pascals test pressure for both single-family and multifamily construction in Climate Zones 3-8. Other programs (LEED, ASHRAE 189, ASHRAE 62.2) have similar or tighter compartmentalization requirements, driving the need for easier and more effective methods of compartmentalization in multifamily buildings. Builders and practitioners have found that fire-resistance rated wall assemblies are a major source of difficulty in air sealing/compartmentalization, particularly in townhouse construction. This problem is exacerbated when garages are “tucked in” to the units and living space is located over the garages. In this project, Building Science Corporation examined the taping of exterior sheathing details to improve air sealing results in townhouse and multifamily construction, when coupled with a better understanding of air leakage pathways. Current approaches are cumbersome, expensive, time consuming, and ineffective; these details were proposed as a more effective and efficient method. The effectiveness of these air sealing methods was tested with blower door testing, including “nulled” or “guarded” testing (adjacent units run at equal test pressure to null out inter-unit air leakage, or “pressure neutralization”). Pressure diagnostics were used to evaluate unit-to-unit connections and series leakage pathways (i.e., air leakage from exterior, into the fire-resistance rated wall assembly, and to the interior).

  4. The Golgi apparatus regulates cGMP-dependent protein kinase I compartmentation and proteolysis.

    PubMed

    Kato, Shin; Chen, Jingsi; Cornog, Katherine H; Zhang, Huili; Roberts, Jesse D

    2015-06-01

    cGMP-dependent protein kinase I (PKGI) is an important effector of cGMP signaling that regulates vascular smooth muscle cell (SMC) phenotype and proliferation. PKGI has been detected in the perinuclear region of cells, and recent data indicate that proprotein convertases (PCs) typically resident in the Golgi apparatus (GA) can stimulate PKGI proteolysis and generate a kinase fragment that localizes to the nucleus and regulates gene expression. However, the role of the endomembrane system in PKGI compartmentation and processing is unknown. Here, we demonstrate that PKGI colocalizes with endoplasmic reticulum (ER), ER-Golgi intermediate compartment, GA cisterna, and trans-Golgi network proteins in pulmonary artery SMC and cell lines. Moreover, PKGI localizes with furin, a trans-Golgi network-resident PC known to cleave PKGI. ER protein transport influences PKGI localization because overexpression of a constitutively inactive Sar1 transgene caused PKGI retention in the ER. Additionally, PKGI appears to reside within the GA because PKGI immunoreactivity was determined to be resistant to cytosolic proteinase K treatment in live cells. The GA appears to play a role in PKGI proteolysis because overexpression of inositol 1,4,5-trisphosphate receptor-associated cGMP kinase substrate, not only tethered heterologous PKGI-β to the ER and decreased its localization to the GA, but also diminished PKGI proteolysis and nuclear translocation. Also, inhibiting intra-GA protein transport with monensin was observed to decrease PKGI cleavage. These studies detail a role for the endomembrane system in regulating PKGI compartmentation and proteolysis. Moreover, they support the investigation of mechanisms regulating PKGI-dependent nuclear cGMP signaling in the pulmonary vasculature with Golgi dysfunction. PMID:25855081

  5. The Golgi apparatus regulates cGMP-dependent protein kinase I compartmentation and proteolysis

    PubMed Central

    Kato, Shin; Chen, Jingsi; Cornog, Katherine H.; Zhang, Huili

    2015-01-01

    cGMP-dependent protein kinase I (PKGI) is an important effector of cGMP signaling that regulates vascular smooth muscle cell (SMC) phenotype and proliferation. PKGI has been detected in the perinuclear region of cells, and recent data indicate that proprotein convertases (PCs) typically resident in the Golgi apparatus (GA) can stimulate PKGI proteolysis and generate a kinase fragment that localizes to the nucleus and regulates gene expression. However, the role of the endomembrane system in PKGI compartmentation and processing is unknown. Here, we demonstrate that PKGI colocalizes with endoplasmic reticulum (ER), ER-Golgi intermediate compartment, GA cisterna, and trans-Golgi network proteins in pulmonary artery SMC and cell lines. Moreover, PKGI localizes with furin, a trans-Golgi network-resident PC known to cleave PKGI. ER protein transport influences PKGI localization because overexpression of a constitutively inactive Sar1 transgene caused PKGI retention in the ER. Additionally, PKGI appears to reside within the GA because PKGI immunoreactivity was determined to be resistant to cytosolic proteinase K treatment in live cells. The GA appears to play a role in PKGI proteolysis because overexpression of inositol 1,4,5-trisphosphate receptor-associated cGMP kinase substrate, not only tethered heterologous PKGI-β to the ER and decreased its localization to the GA, but also diminished PKGI proteolysis and nuclear translocation. Also, inhibiting intra-GA protein transport with monensin was observed to decrease PKGI cleavage. These studies detail a role for the endomembrane system in regulating PKGI compartmentation and proteolysis. Moreover, they support the investigation of mechanisms regulating PKGI-dependent nuclear cGMP signaling in the pulmonary vasculature with Golgi dysfunction. PMID:25855081

  6. Organic tissues, graphite, and hydrocarbons in host rocks of the Rum Jungle Uranium Field, northern Australia

    USGS Publications Warehouse

    Foster, C.B.; Robbins, E.I.; Bone, Y.

    1990-01-01

    The Rum Jungle Uranium field consists of at least six early Proterozoic deposits that have been mined either for uranium and/or the associated base and precious metals. Organic matter in the host rocks of the Whites Formation and Coomalie Dolomite is now predominantly graphite, consistent with the metamorphic history of these rocks. For nine samples, the mean total organic carbon content is high (3.9 wt%) and ranged from 0.33 to 10.44 wt%. Palynological extracts from the host rocks include black, filamentous, stellate (Eoastrion-like), and spherical morphotypes, which are typical of early Proterozoic microbiota. The colour, abundance, and shapes of these morphotypes reflect the thermal history, organic richness, and probable lacustrine biofacies of the host rocks. Routine analysis of rock thin sections and of palynological residues shows that mineral grains in some of the host rocks are coated with graphitized organic matter. The grain coating is presumed to result from ultimate thermal degradation of a petroleum phase that existed prior to metamorphism. Hydrocarbons are, however, still present in fluid inclusions within carbonates of the Coomalie Dolomite and lower Whites Formation. The fluid inclusions fluoresce dull orange in blue-light excitation and their hydrocarbon content is confirmed by gas chromatography of whole-rock extracts. Preliminary analysis of the oil suggests that it is migrated, and because it has escaped graphitization through metamorphism it is probably not of early Proterozoic age. The presence of live oil is consistent with fluid inclusion data that suggest subsequent, low-temperature brine migration through the rocks. The present observations support earlier suggestions that organic matter in the host formations trapped uranium to form protore. Subsequent fluid migrations probably brought additional uranium and other metals to these formations, and the organic matter provided a reducing environment for entrapment. ?? 1990.

  7. Reproductive tract infections in rural women from the highlands, jungle, and coastal regions of Peru.

    PubMed Central

    García, Patricia J.; Chavez, Susana; Feringa, Barbara; Chiappe, Marina; Li, Weili; Jansen, Kathrin U.; Cárcamo, César; Holmes, King K.

    2004-01-01

    OBJECTIVE: To define the prevalences and manifestations of reproductive tract infections (RTIs) in rural Peruvian women. METHODS: During 1997-98, we visited 18 rural districts in coastal, highlands, and jungle regions of Peru. We administered standardized questionnaires and pelvic examinations to members of women's community-based organizations; and collected vaginal fluid for pH, amine odour, Gram stain, microscopy, and culture for Trichomonas vaginalis; cervical specimens for Chlamydia trachomatis, Neisseria gonorrhoeae; human papilloma virus (HPV) by polymerase chain reaction (PCR) assays, and blood for syphilis serology. FINDINGS: The 754 participants averaged 36.9 years of age and 1.7 sex partners ever; 77% reported symptoms indicative of RTIs; 51% and 26% reported their symptoms spontaneously or only with specific questioning, respectively. Symptoms reported spontaneously included abnormal vaginal discharge (29.3% and 22.9%, respectively). One or more RTIs, found in 70.4% of participants, included bacterial vaginosis (43.7%), trichomoniasis (16.5%), vulvovaginal candidiasis (4.5%), chlamydial infection (6.8%), gonorrhoea (1.2%), syphilis seropositivity (1.7%), cervical HPV infection (4.9%), and genital warts or ulcers (2.8%). Of 715 adequate Pap smears, 7 revealed cancer, 4 high-grade squamous intra-epithelial lesions (SIL) and 15 low-grade SIL. Clinical algorithms had very low sensitivity and predictive values for cervical infection, but over half the women with symptoms of malodorous vaginal discharge, signs of abnormal vaginal discharge, or both, had bacterial vaginosis or trichomoniasis. CONCLUSION: Overall, 77% of women had symptoms indicative of RTIs, and 70% had objective evidence of one or more RTIs. Women with selected symptoms and signs of vaginal infection could benefit from standard metronidazole therapy. PMID:15508193

  8. Compartmental Innervation of the Superior Oblique Muscle in Mammals

    PubMed Central

    Le, Alan; Poukens, Vadims; Ying, Howard; Rootman, Daniel; Goldberg, Robert A.; Demer, Joseph L.

    2015-01-01

    Purpose Intramuscular innervation of mammalian horizontal rectus extraocular muscles (EOMs) is compartmental. We sought evidence of similar compartmental innervation of the superior oblique (SO) muscle. Methods Three fresh bovine orbits and one human orbit were dissected to trace continuity of SO muscle and tendon fibers to the scleral insertions. Whole orbits were also obtained from four humans (two adults, a 17-month-old child, and a 33-week stillborn fetus), two rhesus monkeys, one rabbit, and one cow. Orbits were formalin fixed, embedded whole in paraffin, serially sectioned in the coronal plane at 10-μm thickness, and stained with Masson trichrome. Extraocular muscle fibers and branches of the trochlear nerve (CN4) were traced in serial sections and reconstructed in three dimensions. Results In the human, the lateral SO belly is in continuity with tendon fibers inserting more posteriorly on the sclera for infraducting mechanical advantage, while the medial belly is continuous with anteriorly inserting fibers having mechanical advantage for incycloduction. Fibers in the monkey superior SO insert more posteriorly on the sclera to favor infraduction, while the inferior portion inserts more anteriorly to favor incycloduction. In all species, CN4 bifurcates prior to penetrating the SO belly. Each branch innervates a nonoverlapping compartment of EOM fibers, consisting of medial and lateral compartments in humans and monkeys, and superior and inferior compartments in cows and rabbits. Conclusions The SO muscle of humans and other mammals is compartmentally innervated in a manner that could permit separate CN4 branches to selectively influence vertical versus torsional action. PMID:26426404

  9. Functional Compartmentalization of the Human Superficial Masseter Muscle

    PubMed Central

    Guzmán-Venegas, Rodrigo A.; Biotti Picand, Jorge L.; de la Rosa, Francisco J. Berral

    2015-01-01

    Some muscles have demonstrated a differential recruitment of their motor units in relation to their location and the nature of the motor task performed; this involves functional compartmentalization. There is little evidence that demonstrates the presence of a compartmentalization of the superficial masseter muscle during biting. The aim of this study was to describe the topographic distribution of the activity of the superficial masseter (SM) muscle’s motor units using high-density surface electromyography (EMGs) at different bite force levels. Twenty healthy natural dentate participants (men: 4; women: 16; age 20±2 years; mass: 60±12 kg, height: 163±7 cm) were selected from 316 volunteers and included in this study. Using a gnathodynamometer, bites from 20 to 100% maximum voluntary bite force (MVBF) were randomly requested. Using a two-dimensional grid (four columns, six electrodes) located on the dominant SM, EMGs in the anterior, middle-anterior, middle-posterior and posterior portions were simultaneously recorded. In bite ranges from 20 to 60% MVBF, the EMG activity was higher in the anterior than in the posterior portion (p-value = 0.001).The center of mass of the EMG activity was displaced towards the posterior part when bite force increased (p-value = 0.001). The topographic distribution of EMGs was more homogeneous at high levels of MVBF (p-value = 0.001). The results of this study show that the superficial masseter is organized into three functional compartments: an anterior, a middle and a posterior compartment. However, this compartmentalization is only seen at low levels of bite force (20–60% MVBF). PMID:25692977

  10. Analytical properties of a three-compartmental dynamical demographic model

    NASA Astrophysics Data System (ADS)

    Postnikov, E. B.

    2015-07-01

    The three-compartmental demographic model by Korotaeyv-Malkov-Khaltourina, connecting population size, economic surplus, and education level, is considered from the point of view of dynamical systems theory. It is shown that there exist two integrals of motion, which enables the system to be reduced to one nonlinear ordinary differential equation. The study of its structure provides analytical criteria for the dominance ranges of the dynamics of Malthus and Kremer. Additionally, the particular ranges of parameters enable the derived general ordinary differential equations to be reduced to the models of Gompertz and Thoularis-Wallace.

  11. Dynamic behaviors of a class of HIV compartmental models

    NASA Astrophysics Data System (ADS)

    Chen, Xiaoyan; Huang, Lihong; Yu, Pei

    2015-06-01

    Based on heterogeneities in drug efficacy (either spatial or phenotypic), two HIV compartmental models were proposed in Callaway and Perelson (2002) to study the HIV virus dynamics under drug treatment. In this paper, we provide a global analysis on the two models, including the positivity and boundedness of solutions and the global stability of equilibrium solutions. In particular, we show that when the basic reproduction number R0 ⩽ 1 (for which the infection equilibrium does not exist), the infection-free equilibrium is globally asymptotically stable; while when R0 > 1 (for which the infection equilibrium exists), the infection equilibrium is globally asymptotically stable.

  12. Super-resolution Microscopy Reveals Compartmentalization of Peroxisomal Membrane Proteins.

    PubMed

    Galiani, Silvia; Waithe, Dominic; Reglinski, Katharina; Cruz-Zaragoza, Luis Daniel; Garcia, Esther; Clausen, Mathias P; Schliebs, Wolfgang; Erdmann, Ralf; Eggeling, Christian

    2016-08-12

    Membrane-associated events during peroxisomal protein import processes play an essential role in peroxisome functionality. Many details of these processes are not known due to missing spatial resolution of technologies capable of investigating peroxisomes directly in the cell. Here, we present the use of super-resolution optical stimulated emission depletion microscopy to investigate with sub-60-nm resolution the heterogeneous spatial organization of the peroxisomal proteins PEX5, PEX14, and PEX11 around actively importing peroxisomes, showing distinct differences between these peroxins. Moreover, imported protein sterol carrier protein 2 (SCP2) occupies only a subregion of larger peroxisomes, highlighting the heterogeneous distribution of proteins even within the peroxisome. Finally, our data reveal subpopulations of peroxisomes showing only weak colocalization between PEX14 and PEX5 or PEX11 but at the same time a clear compartmentalized organization. This compartmentalization, which was less evident in cases of strong colocalization, indicates dynamic protein reorganization linked to changes occurring in the peroxisomes. Through the use of multicolor stimulated emission depletion microscopy, we have been able to characterize peroxisomes and their constituents to a yet unseen level of detail while maintaining a highly statistical approach, paving the way for equally complex biological studies in the future. PMID:27311714

  13. From Compartmentalized to Agent-based Models of Epidemics

    NASA Astrophysics Data System (ADS)

    Macal, Charles

    Supporting decisions in the throes of an impending epidemic poses distinct technical challenges arising from the uncertainties in modeling disease propagation processes and the need for producing timely answers to policy questions. Compartmental models, because of their relative simplicity, produce timely information, but often do not include the level of fidelity of the information needed to answer specific policy questions. Highly granular agent-based simulations produce an extensive amount of information on all aspects of a simulated epidemic, yet complex models often cannot produce this information in a timely manner. We propose a two-phased approach to addressing the tradeoff between model complexity and the speed at which models can be used to answer to questions about an impending outbreak. In the first phase, in advance of an epidemic, ensembles of highly granular agent-based simulations are run over the entire parameter space, characterizing the space of possible model outcomes and uncertainties. Meta-models are derived that characterize model outcomes as dependent on uncertainties in disease parameters, data, and structural relationships. In the second phase, envisioned as during an epidemic, the meta-model is run in combination with compartmental models, which can be run very quickly. Model outcomes are compared as a basis for establishing uncertainties in model forecasts. This work is supported by the U.S. Department of Energy under Contract number DE-AC02-06CH11357 and National Science Foundation (NSF) RAPID Award DEB-1516428.

  14. Directed evolution of polymerase function by compartmentalized self-replication.

    PubMed

    Ghadessy, F J; Ong, J L; Holliger, P

    2001-04-10

    We describe compartmentalized self-replication (CSR), a strategy for the directed evolution of enzymes, especially polymerases. CSR is based on a simple feedback loop consisting of a polymerase that replicates only its own encoding gene. Compartmentalization serves to isolate individual self-replication reactions from each other. In such a system, adaptive gains directly (and proportionally) translate into genetic amplification of the encoding gene. CSR has applications in the evolution of polymerases with novel and useful properties. By using three cycles of CSR, we obtained variants of Taq DNA polymerase with 11-fold higher thermostability than the wild-type enzyme or with a >130-fold increased resistance to the potent inhibitor heparin. Insertion of an extra stage into the CSR cycle before the polymerase reaction allows its application to enzymes other than polymerases. We show that nucleoside diphosphate kinase and Taq polymerase can form such a cooperative CSR cycle based on reciprocal catalysis, whereby nucleoside diphosphate kinase produces the substrates required for the replication of its own gene. We also find that in CSR the polymerase genes themselves evolve toward more efficient replication. Thus, polymerase genes and their encoded polypeptides cooperate to maximize postselection copy number. CSR should prove useful for the directed evolution of enzymes, particularly DNA or RNA polymerases, as well as for the design and study of in vitro self-replicating systems mimicking prebiotic evolution and viral replication. PMID:11274352

  15. Super-resolution Microscopy Reveals Compartmentalization of Peroxisomal Membrane Proteins*

    PubMed Central

    Galiani, Silvia; Waithe, Dominic; Reglinski, Katharina; Cruz-Zaragoza, Luis Daniel; Garcia, Esther; Clausen, Mathias P.; Schliebs, Wolfgang; Erdmann, Ralf; Eggeling, Christian

    2016-01-01

    Membrane-associated events during peroxisomal protein import processes play an essential role in peroxisome functionality. Many details of these processes are not known due to missing spatial resolution of technologies capable of investigating peroxisomes directly in the cell. Here, we present the use of super-resolution optical stimulated emission depletion microscopy to investigate with sub-60-nm resolution the heterogeneous spatial organization of the peroxisomal proteins PEX5, PEX14, and PEX11 around actively importing peroxisomes, showing distinct differences between these peroxins. Moreover, imported protein sterol carrier protein 2 (SCP2) occupies only a subregion of larger peroxisomes, highlighting the heterogeneous distribution of proteins even within the peroxisome. Finally, our data reveal subpopulations of peroxisomes showing only weak colocalization between PEX14 and PEX5 or PEX11 but at the same time a clear compartmentalized organization. This compartmentalization, which was less evident in cases of strong colocalization, indicates dynamic protein reorganization linked to changes occurring in the peroxisomes. Through the use of multicolor stimulated emission depletion microscopy, we have been able to characterize peroxisomes and their constituents to a yet unseen level of detail while maintaining a highly statistical approach, paving the way for equally complex biological studies in the future. PMID:27311714

  16. Compartmentation and equilibration of abscisic acid in isolated Xanthium cells

    SciTech Connect

    Bray, E.A.; Zeevaart, J.A.D.

    1986-01-01

    The compartmentation of endogenous abscisic acid (ABA), applied (+/-)-(/sup 3/H)ABA, and (+/-)-trans-ABA was measured in isolated mesophyll cells of the Chicago strain of Xanthium strumarium L. The release of ABA to the medium in the presence or absence of DMSO was used to determine the equilibration of ABA in the cells. It was found that a greater percentage of the (+/-)-(/sup 3/H)ABA and the (+/-)-trans-ABA was released into the medium than of the endogenous ABA, indicating that applied ABA did not equilibrate with the endogenous material. Therefore, in further investigations only the compartmentation of endogenous ABA was studied. Endogenous ABA was released from Xanthium cells according to the pH gradients among the various cellular compartments. Thus, darkness, high external pH, KNO/sub 2/, and drought-stress all increased the efflux of ABA from the cells. Efflux of ABA from the cells in the presence of 0.6 M mannitol occurred within 30 seconds, but only 8% of the endogenous material was released during the 20 minute treatment.

  17. Directed evolution of polymerase function by compartmentalized self-replication

    PubMed Central

    Ghadessy, Farid J.; Ong, Jennifer L.; Holliger, Philipp

    2001-01-01

    We describe compartmentalized self-replication (CSR), a strategy for the directed evolution of enzymes, especially polymerases. CSR is based on a simple feedback loop consisting of a polymerase that replicates only its own encoding gene. Compartmentalization serves to isolate individual self-replication reactions from each other. In such a system, adaptive gains directly (and proportionally) translate into genetic amplification of the encoding gene. CSR has applications in the evolution of polymerases with novel and useful properties. By using three cycles of CSR, we obtained variants of Taq DNA polymerase with 11-fold higher thermostability than the wild-type enzyme or with a >130-fold increased resistance to the potent inhibitor heparin. Insertion of an extra stage into the CSR cycle before the polymerase reaction allows its application to enzymes other than polymerases. We show that nucleoside diphosphate kinase and Taq polymerase can form such a cooperative CSR cycle based on reciprocal catalysis, whereby nucleoside diphosphate kinase produces the substrates required for the replication of its own gene. We also find that in CSR the polymerase genes themselves evolve toward more efficient replication. Thus, polymerase genes and their encoded polypeptides cooperate to maximize postselection copy number. CSR should prove useful for the directed evolution of enzymes, particularly DNA or RNA polymerases, as well as for the design and study of in vitro self-replicating systems mimicking prebiotic evolution and viral replication. PMID:11274352

  18. Building America Case Study: Field Testing of Compartmentalization Methods for Multifamily Construction (Fact Sheet)

    SciTech Connect

    Not Available

    2015-01-01

    The 2012 IECC has an airtightness requirement of 3 air changes per hour at 50 Pascals test pressure for both single family and multifamily construction in Climate Zones 3-8. Other programs (LEED, ASHRAE 189, ASHRAE 62.2) have similar or tighter compartmentalization requirements, thus driving the need for easier and more effective methods of compartmentalization in multifamily buildings.

  19. 21 CFR 888.3535 - Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Knee joint femorotibial (uni-compartmental) metal... Devices § 888.3535 Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis. (a) Identification. A knee joint femorotibial (uni-compartmental) metal/polymer...

  20. 21 CFR 888.3535 - Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Knee joint femorotibial (uni-compartmental) metal... Devices § 888.3535 Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis. (a) Identification. A knee joint femorotibial (uni-compartmental) metal/polymer...

  1. 21 CFR 888.3535 - Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Knee joint femorotibial (uni-compartmental) metal... Devices § 888.3535 Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis. (a) Identification. A knee joint femorotibial (uni-compartmental) metal/polymer...

  2. Hydrological Compartmentalization: A Grand Challenge in the Critical Zone

    NASA Astrophysics Data System (ADS)

    McDonnell, J.; Evaristo, J. A.; Orlowski, N.; Jasechko, S.

    2015-12-01

    Current terrestrial biosphere models assume that plant transpiration, groundwater and streamflow are all sourced and mediated by the same well mixed soil reservoir. Recent stable water isotope data from Oregon and Mexico and now global meta-analysis and remote sensing measurements have all shown evidence of hydrological compartmentalization: a mobile compartment that forms groundwater and streamflow and a poorly mobile compartment that supplies plant transpiration. The way we now measure and model this poorly mobile water is a grand challenge for understanding subsurface mixing, water residence time, and its interaction and feedback to ecosystem processes. Here we review the latest results from this work and outline some of the future research challenges for understanding soil-plant-atmospheric interactions between the bedrock and the boundary layer.

  3. Hydrological Compartmentalization: A Grand Challenge in the Critical Zone

    NASA Astrophysics Data System (ADS)

    McDonnell, J.; Evaristo, J. A.; Orlowski, N.; Jasechko, S.

    2014-12-01

    Current terrestrial biosphere models assume that plant transpiration, groundwater and streamflow are all sourced and mediated by the same well mixed soil reservoir. Recent stable water isotope data from Oregon and Mexico and now global meta-analysis and remote sensing measurements have all shown evidence of hydrological compartmentalization: a mobile compartment that forms groundwater and streamflow and a poorly mobile compartment that supplies plant transpiration. The way we now measure and model this poorly mobile water is a grand challenge for understanding subsurface mixing, water residence time, and its interaction and feedback to ecosystem processes. Here we review the latest results from this work and outline some of the future research challenges for understanding soil-plant-atmospheric interactions between the bedrock and the boundary layer.

  4. The human NAD metabolome: Functions, metabolism and compartmentalization

    PubMed Central

    Nikiforov, Andrey; Kulikova, Veronika; Ziegler, Mathias

    2015-01-01

    Abstract The metabolism of NAD has emerged as a key regulator of cellular and organismal homeostasis. Being a major component of both bioenergetic and signaling pathways, the molecule is ideally suited to regulate metabolism and major cellular events. In humans, NAD is synthesized from vitamin B3 precursors, most prominently from nicotinamide, which is the degradation product of all NAD-dependent signaling reactions. The scope of NAD-mediated regulatory processes is wide including enzyme regulation, control of gene expression and health span, DNA repair, cell cycle regulation and calcium signaling. In these processes, nicotinamide is cleaved from NAD+ and the remaining ADP-ribosyl moiety used to modify proteins (deacetylation by sirtuins or ADP-ribosylation) or to generate calcium-mobilizing agents such as cyclic ADP-ribose. This review will also emphasize the role of the intermediates in the NAD metabolome, their intra- and extra-cellular conversions and potential contributions to subcellular compartmentalization of NAD pools. PMID:25837229

  5. Organs-on-a-chip: a focus on compartmentalized microdevices.

    PubMed

    Moraes, Christopher; Mehta, Geeta; Lesher-Perez, Sasha Cai; Takayama, Shuichi

    2012-06-01

    Advances in microengineering technologies have enabled a variety of insights into biomedical sciences that would not have been possible with conventional techniques. Engineering microenvironments that simulate in vivo organ systems may provide critical insight into the cellular basis for pathophysiologies, development, and homeostasis in various organs, while curtailing the high experimental costs and complexities associated with in vivo studies. In this article, we aim to survey recent attempts to extend tissue-engineered platforms toward simulating organ structure and function, and discuss the various approaches and technologies utilized in these systems. We specifically focus on microtechnologies that exploit phenomena associated with compartmentalization to create model culture systems that better represent the in vivo organ microenvironment. PMID:22065201

  6. Compartmentalization of NO signaling cascade in skeletal muscles

    SciTech Connect

    Buchwalow, Igor B. . E-mail: buchwalo@uni-muenster.de; Minin, Evgeny A.; Samoilova, Vera E.; Boecker, Werner; Wellner, Maren; Schmitz, Wilhelm; Neumann, Joachim

    2005-05-06

    Skeletal muscle functions regulated by NO are now firmly established. However, the literature on the compartmentalization of NO signaling in myocytes is highly controversial. To address this issue, we examined localization of enzymes engaged in L-arginine-NO-cGMP signaling in the rat quadriceps muscle. Employing immunocytochemical labeling complemented with tyramide signal amplification and electron microscopy, we found NO synthase expressed not only in the sarcolemma, but also along contractile fibers, in the sarcoplasmic reticulum and mitochondria. The expression pattern of NO synthase in myocytes showed striking parallels with the enzymes engaged in L-arginine-NO-cGMP signaling (arginase, phosphodiesterase, and soluble guanylyl cyclase). Our findings are indicative of an autocrine fashion of NO signaling in skeletal muscles at both cellular and subcellular levels, and challenge the notion that the NO generation is restricted to the sarcolemma.

  7. Partitioning Variability of a Compartmentalized In Vitro Transcriptional Thresholding Circuit.

    PubMed

    Kapsner, Korbinian; Simmel, Friedrich C

    2015-10-16

    Encapsulation of in vitro biochemical reaction circuits into small, cell-sized compartments can result in considerable variations in the dynamical properties of the circuits. As a model system, we here investigate a simple in vitro transcriptional reaction circuit, which generates an ultrasensitive fluorescence response when the concentration of an RNA transcript reaches a preset threshold. The reaction circuit is compartmentalized into spherical water-in-oil microemulsion droplets, and the reaction progress is monitored by fluorescence microscopy. A quantitative statistical analysis of thousands of individual droplets ranging in size from a few up to 20 μm reveals a strong variability in effective RNA production rates, which by computational modeling is traced back to a larger-than-Poisson variability in RNAP activities in the droplets. The noise level in terms of the noise strength (the Fano factor) is strongly dependent on the ratio between transcription templates and polymerases, and increases for higher template concentrations. PMID:25974035

  8. Sharpness of Spike Initiation in Neurons Explained by Compartmentalization

    PubMed Central

    Brette, Romain

    2013-01-01

    In cortical neurons, spikes are initiated in the axon initial segment. Seen at the soma, they appear surprisingly sharp. A standard explanation is that the current coming from the axon becomes sharp as the spike is actively backpropagated to the soma. However, sharp initiation of spikes is also seen in the input–output properties of neurons, and not only in the somatic shape of spikes; for example, cortical neurons can transmit high frequency signals. An alternative hypothesis is that Na channels cooperate, but it is not currently supported by direct experimental evidence. I propose a simple explanation based on the compartmentalization of spike initiation. When Na channels are placed in the axon, the soma acts as a current sink for the Na current. I show that there is a critical distance to the soma above which an instability occurs, so that Na channels open abruptly rather than gradually as a function of somatic voltage. PMID:24339755

  9. Apartment Compartmentalization With an Aerosol-Based Sealing Process

    SciTech Connect

    Maxwell, S.; Berger, D.; Harrington, C.

    2015-03-01

    Air sealing of building enclosures is a difficult and time-consuming process. Current methods in new construction require laborers to physically locate small and sometimes large holes in multiple assemblies and then manually seal each of them. The innovation demonstrated under this research study was the automated air sealing and compartmentalization of buildings through the use of an aerosolized sealant, developed by the Western Cooling Efficiency Center at University of California Davis. CARB sought to demonstrate this new technology application in a multifamily building in Queens, NY. The effectiveness of the sealing process was evaluated by three methods: air leakage testing of overall apartment before and after sealing, point-source testing of individual leaks, and pressure measurements in the walls of the target apartment during sealing.

  10. A Self-compartmentalizing Hexamer Serine Protease from Pyrococcus Horikoshii

    PubMed Central

    Menyhárd, Dóra K.; Kiss-Szemán, Anna; Tichy-Rács, Éva; Hornung, Balázs; Rádi, Krisztina; Szeltner, Zoltán; Domokos, Klarissza; Szamosi, Ilona; Náray-Szabó, Gábor; Polgár, László; Harmat, Veronika

    2013-01-01

    Oligopeptidases impose a size limitation on their substrates, the mechanism of which has long been under debate. Here we present the structure of a hexameric serine protease, an oligopeptidase from Pyrococcus horikoshii (PhAAP), revealing a complex, self-compartmentalized inner space, where substrates may access the monomer active sites passing through a double-gated “check-in” system, first passing through a pore on the hexamer surface and then turning to enter through an even smaller opening at the monomers' domain interface. This substrate screening strategy is unique within the family. We found that among oligopeptidases, a residue of the catalytic apparatus is positioned near an amylogenic β-edge, which needs to be protected to prevent aggregation, and we found that different oligopeptidases use different strategies to achieve such an end. We propose that self-assembly within the family results in characteristically different substrate selection mechanisms coupled to different multimerization states. PMID:23632025

  11. Molecular Mechanisms of Compartmentalization and Biomineralization in Magnetotactic Bacteria

    PubMed Central

    Komeili, Arash

    2011-01-01

    Magnetotactic bacteria are remarkable organisms with the ability to exploit the earth’s magnetic field for navigational purposes. To do this, they build specialized compartments called magnetosomes that consist of a lipid membrane and a crystalline magnetic mineral. These organisms have the potential to serve as models for the study of compartmentalization as well as biomineralization in bacteria. Additionally, they offer the opportunity to design applications that take advantage of the particular properties of magnetosomes. In recent years, a sustained effort to identify the molecular basis of this process has resulted in a clearer understanding of the magnetosome formation and biomineralization. Here, I present an overview of magnetotactic bacteria and explore the possible molecular mechanisms of membrane remodeling, protein sorting, cytoskeletal organization, iron transport and biomineralization that lead to the formation of a functional magnetosome organelle. PMID:22092030

  12. Evolution of energy metabolism and its compartmentation in Kinetoplastida

    PubMed Central

    Hannaert, Véronique; Bringaud, Frédéric; Opperdoes, Fred R; Michels, Paul AM

    2003-01-01

    Kinetoplastida are protozoan organisms that probably diverged early in evolution from other eukaryotes. They are characterized by a number of unique features with respect to their energy and carbohydrate metabolism. These organisms possess peculiar peroxisomes, called glycosomes, which play a central role in this metabolism; the organelles harbour enzymes of several catabolic and anabolic routes, including major parts of the glycolytic and pentosephosphate pathways. The kinetoplastid mitochondrion is also unusual with regard to both its structural and functional properties. In this review, we describe the unique compartmentation of metabolism in Kinetoplastida and the metabolic properties resulting from this compartmentation. We discuss the evidence for our recently proposed hypothesis that a common ancestor of Kinetoplastida and Euglenida acquired a photosynthetic alga as an endosymbiont, contrary to the earlier notion that this event occurred at a later stage of evolution, in the Euglenida lineage alone. The endosymbiont was subsequently lost from the kinetoplastid lineage but, during that process, some of its pathways of energy and carbohydrate metabolism were sequestered in the kinetoplastid peroxisomes, which consequently became glycosomes. The evolution of the kinetoplastid glycosomes and the possible selective advantages of these organelles for Kinetoplastida are discussed. We propose that the possession of glycosomes provided metabolic flexibility that has been important for the organisms to adapt easily to changing environmental conditions. It is likely that metabolic flexibility has been an important selective advantage for many kinetoplastid species during their evolution into the highly successful parasites today found in many divergent taxonomic groups. Also addressed is the evolution of the kinetoplastid mitochondrion, from a supposedly pluripotent organelle, attributed to a single endosymbiotic event that resulted in all mitochondria and

  13. Approximating the stabilization of cellular metabolism by compartmentalization.

    PubMed

    Fürtauer, Lisa; Nägele, Thomas

    2016-06-01

    Biochemical regulation in compartmentalized metabolic networks is highly complex and non-intuitive. This is particularly true for cells of higher plants showing one of the most compartmentalized cellular structures across all kingdoms of life. The interpretation and testable hypothesis generation from experimental data on such complex systems is a challenging step in biological research and biotechnological applications. While it is known that subcellular compartments provide defined reaction spaces within a cell allowing for the tight coordination of complex biochemical reaction sequences, its role in the coordination of metabolic signals during metabolic reprogramming due to environmental fluctuations is less clear. In the present study, we numerically analysed the effects of environmental fluctuations in a subcellular metabolic network with regard to the stability of an experimentally observed steady state in the genetic model plant Arabidopsis thaliana. Applying a method for kinetic parameter normalization, several millions of probable enzyme kinetic parameter constellations were simulated and evaluated with regard to the stability information of the metabolic homeostasis. Information about the stability of the metabolic steady state was derived from real parts of eigenvalues of Jacobian matrices. Our results provide evidence for a differential stabilizing contribution of different subcellular compartments. We could identify stabilizing and destabilizing network components which we could classify according to their subcellular localization. The findings prove that a highly dynamic interplay between intracellular compartments is preliminary for an efficient stabilization of a metabolic homeostasis after environmental perturbation. Further, our results provide evidence that feedback-inhibition originating from the cytosol and plastid seem to stabilize the sucrose homeostasis more efficiently than vacuolar control. In summary, our results indicate stabilizing and

  14. Virus-Mediated Compartmentalization of the Host Translational Machinery

    PubMed Central

    Desmet, Emily A.; Anguish, Lynne J.

    2014-01-01

    ABSTRACT Viruses require the host translational apparatus to synthesize viral proteins. Host stress response mechanisms that suppress translation, therefore, represent a significant obstacle that viruses must overcome. Here, we report a strategy whereby the mammalian orthoreoviruses compartmentalize the translational machinery within virus-induced inclusions known as viral factories (VF). VF are the sites of reovirus replication and assembly but were thought not to contain ribosomes. It was assumed viral mRNAs exited the VF to undergo translation by the cellular machinery, and proteins reentered the factory to participate in assembly. Here, we used ribopuromycylation to visualize active translation in infected cells. These studies revealed that active translation occurs within VF and that ribosomal subunits and proteins required for translation initiation, elongation, termination, and recycling localize to the factory. Interestingly, we observed components of the 43S preinitiation complex (PIC) concentrating primarily at factory margins, suggesting a spatial and/or dynamic organization of translation within the VF. Similarly, the viral single-stranded RNA binding protein σNS localized to the factory margins and had a tubulovesicular staining pattern that extended a short distance from the margins of the factories and colocalized with endoplasmic reticulum (ER) markers. Consistent with these colocalization studies, σNS was found to associate with both eukaryotic translation initiation factor 3 subunit A (eIF3A) and the ribosomal subunit pS6R. Together, these findings indicate that σNS functions to recruit 43S PIC machinery to the primary site of viral translation within the viral factory. Pathogen-mediated compartmentalization of the translational apparatus provides a novel mechanism by which viruses might avoid host translational suppression. PMID:25227463

  15. Dynamin regulates metaphase furrow formation and plasma membrane compartmentalization in the syncytial Drosophila embryo

    PubMed Central

    Rikhy, Richa; Mavrakis, Manos; Lippincott-Schwartz, Jennifer

    2015-01-01

    ABSTRACT The successive nuclear division cycles in the syncytial Drosophila embryo are accompanied by ingression and regression of plasma membrane furrows, which surround individual nuclei at the embryo periphery, playing a central role in embryo compartmentalization prior to cellularization. Here, we demonstrate that cell cycle changes in dynamin localization and activity at the plasma membrane (PM) regulate metaphase furrow formation and PM organization in the syncytial embryo. Dynamin was localized on short PM furrows during interphase, mediating endocytosis of PM components. Dynamin redistributed off ingressed PM furrows in metaphase, correlating with stabilized PM components and the associated actin regulatory machinery on long furrows. Acute inhibition of dynamin in the temperature sensitive shibire mutant embryo resulted in morphogenetic consequences in the syncytial division cycle. These included inhibition of metaphase furrow ingression, randomization of proteins normally polarized to intercap PM and disruption of the diffusion barrier separating PM domains above nuclei. Based on these findings, we propose that cell cycle changes in dynamin orchestrate recruitment of actin regulatory machinery for PM furrow dynamics during the early mitotic cycles in the Drosophila embryo. PMID:25661871

  16. Compartmentation of sucrose during radial transfer in mature sorghum culm

    PubMed Central

    Tarpley, Lee; Vietor, Donald M

    2007-01-01

    Background The sucrose that accumulates in the culm of sorghum (Sorghum bicolor (L.) Moench) and other large tropical andropogonoid grasses can be of commercial value, and can buffer assimilate supply during development. Previous study conducted with intact plants showed that sucrose can be radially transferred to the intracellular compartment of mature ripening sorghum internode without being hydrolysed. In this study, culm-infused radiolabelled sucrose was traced between cellular compartments and among related metabolites to determine if the compartmental path of sucrose during radial transfer in culm tissue was symplasmic or included an apoplasmic step. This transfer path was evaluated for elongating and ripening culm tissue of intact plants of two semidwarf grain sorghums. The metabolic path in elongating internode tissue was also evaluated. Results On the day after culm infusion of the tracer sucrose, the specific radioactivity of sucrose recovered from the intracellular compartment of growing axillary-branch tissue was greater (nearly twice) than that in the free space, indicating that sucrose was preferentially transferred through symplasmic routes. In contrast, the sucrose specific radioactivity in the intracellular compartment of the mature (ripening) culm tissue was probably less (about 3/4's) than that in free space indicating that sucrose was preferentially transferred through routes that included an apoplasmic step. In growing internodes of the axillary branch of sorghum, the tritium label initially provided in the fructose moiety of sucrose molecules was largely (81%) recovered in the fructose moiety, indicating that a large portion of sucrose molecules is not hydrolysed and resynthesized during radial transfer. Conclusion During radial transfer of sucrose in ripening internodes of intact sorghum plants, much of the sucrose is transferred intact (without hydrolysis and resynthesis) and primarily through a path that includes an apoplasmic step. In

  17. Mitochondrial genomes of the jungle crow Corvus macrorhynchos (Passeriformes: Corvidae) from shed feathers and a phylogenetic analysis of genus Corvus using mitochondrial protein-coding genes.

    PubMed

    Krzeminska, Urszula; Wilson, Robyn; Rahman, Sadequr; Song, Beng Kah; Seneviratne, Sampath; Gan, Han Ming; Austin, Christopher M

    2016-07-01

    The complete mitochondrial genomes of two jungle crows (Corvus macrorhynchos) were sequenced. DNA was extracted from tissue samples obtained from shed feathers collected in the field in Sri Lanka and sequenced using the Illumina MiSeq Personal Sequencer. Jungle crow mitogenomes have a structural organization typical of the genus Corvus and are 16,927 bp and 17,066 bp in length, both comprising 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal subunit genes, and a non-coding control region. In addition, we complement already available house crow (Corvus spelendens) mitogenome resources by sequencing an individual from Singapore. A phylogenetic tree constructed from Corvidae family mitogenome sequences available on GenBank is presented. We confirm the monophyly of the genus Corvus and propose to use complete mitogenome resources for further intra- and interspecies genetic studies. PMID:26075478

  18. MULTIMEDIA ENVIRONMENTAL DISTRIBUTION OF TOXICS (MEND-TOX): PART I, HYBRID COMPARTMENTAL-SPATIAL MODELING FRAMEWORK

    EPA Science Inventory

    An integrated hybrid spatial-compartmental modeling approach is presented for analyzing the dynamic distribution of chemicals in the multimedia environment. Information obtained from such analysis, which includes temporal chemical concentration profiles in various media, mass ...

  19. Transit times and mean ages for nonautonomous and autonomous compartmental systems

    DOE PAGESBeta

    Rasmussen, Martin; Hastings, Alan; Smith, Matthew J.; Agusto, Folashade B.; Chen-Charpentier, Benito M.; Hoffman, Forrest M.; Jiang, Jiang; Todd-Brown, Katherine E. O.; Wang, Ying; Wang, Ying -Ping; et al

    2016-04-01

    In this study, we develop a theory for transit times and mean ages for nonautonomous compartmental systems. Using the McKendrick–von Förster equation, we show that the mean ages of mass in a compartmental system satisfy a linear nonautonomous ordinary differential equation that is exponentially stable. We then define a nonautonomous version of transit time as the mean age of mass leaving the compartmental system at a particular time and show that our nonautonomous theory generalises the autonomous case. We apply these results to study a nine-dimensional nonautonomous compartmental system modeling the terrestrial carbon cycle, which is a modification of themore » Carnegie–Ames–Stanford approach model, and we demonstrate that the nonautonomous versions of transit time and mean age differ significantly from the autonomous quantities when calculated for that model.« less

  20. Compartmentalization - A Prerequisite for Maintaining and Changing an Identity.

    PubMed

    Rottmann, Philipp; Ward, Thomas; Panke, Sven

    2016-01-01

    The chemical manipulation of DNA is much more convenient than the manipulation of the bioproducts, such as enzymes, that it encodes. The optimization of bioproducts requires cycles of diversification of DNA followed by read-out of the information into the bioproduct. Maintaining the link between the information - the genotype - and the properties of the bioproduct - the phenotype - through some form of compartmentalization is therefore an essential aspect in directed evolution. While the ideal compartment is a biological cell, many projects involving more radical changes in the bioproduct, such as the introduction of novel cofactors, may not be suitable for expression of the information in cells, and alternative in vitro methods have to be applied. Consequently, the possibility to produce simple and advanced micro compartments at high rates and to combine them with the ability to translate the information into proteins represents a unique opportunity to explore demanding enzyme engineering projects that require the evaluation of at least hundreds of thousands of enzyme variants over multiple generations. PMID:27363372

  1. Shape control and compartmentalization in active colloidal cells.

    PubMed

    Spellings, Matthew; Engel, Michael; Klotsa, Daphne; Sabrina, Syeda; Drews, Aaron M; Nguyen, Nguyen H P; Bishop, Kyle J M; Glotzer, Sharon C

    2015-08-25

    Small autonomous machines like biological cells or soft robots can convert energy input into control of function and form. It is desired that this behavior emerges spontaneously and can be easily switched over time. For this purpose we introduce an active matter system that is loosely inspired by biology and which we term an active colloidal cell. The active colloidal cell consists of a boundary and a fluid interior, both of which are built from identical rotating spinners whose activity creates convective flows. Similarly to biological cell motility, which is driven by cytoskeletal components spread throughout the entire volume of the cell, active colloidal cells are characterized by highly distributed energy conversion. We demonstrate that we can control the shape of the active colloidal cell and drive compartmentalization by varying the details of the boundary (hard vs. flexible) and the character of the spinners (passive vs. active). We report buckling of the boundary controlled by the pattern of boundary activity, as well as formation of core-shell and inverted Janus phase-separated configurations within the active cell interior. As the cell size is increased, the inverted Janus configuration spontaneously breaks its mirror symmetry. The result is a bubble-crescent configuration, which alternates between two degenerate states over time and exhibits collective migration of the fluid along the boundary. Our results are obtained using microscopic, non-momentum-conserving Langevin dynamics simulations and verified via a phase-field continuum model coupled to a Navier-Stokes equation. PMID:26253763

  2. Spatiotemporal compartmentalization of key physiological processes during muscle precursor differentiation.

    PubMed

    Ozbudak, Ertugrul M; Tassy, Olivier; Pourquié, Olivier

    2010-03-01

    The development of multicellular organisms is controlled by transcriptional networks. Understanding the role of these networks requires a full understanding of transcriptome regulation during embryogenesis. Several microarray studies have characterized the temporal evolution of the transcriptome during development in different organisms [Wang QT, et al. (2004) Dev Cell 6:133-144; Furlong EE, Andersen EC, Null B, White KP, Scott MP (2001) Science 293:1629-1633; Mitiku N, Baker JC (2007) Dev Cell 13:897-907]. In all cases, however, experiments were performed on whole embryos, thus averaging gene expression among many different tissues. Here, we took advantage of the local synchrony of the differentiation process in the paraxial mesoderm. This approach provides a unique opportunity to study the systems-level properties of muscle differentiation. Using high-resolution, spatiotemporal profiling of the early stages of muscle development in the zebrafish embryo, we identified a major reorganization of the transcriptome taking place in the presomitic mesoderm. We further show that the differentiation process is associated with a striking modular compartmentalization of the transcription of essential components of cellular physiological programs. Particularly, we identify a tight segregation of cell cycle/DNA metabolic processes and translation/oxidative metabolism at the tissue level, highly reminiscent of the yeast metabolic cycle. These results should expand more investigations into the developmental control of metabolism. PMID:20160088

  3. Adaptive and neuroadaptive control for nonnegative and compartmental dynamical systems

    NASA Astrophysics Data System (ADS)

    Volyanskyy, Kostyantyn Y.

    Neural networks have been extensively used for adaptive system identification as well as adaptive and neuroadaptive control of highly uncertain systems. The goal of adaptive and neuroadaptive control is to achieve system performance without excessive reliance on system models. To improve robustness and the speed of adaptation of adaptive and neuroadaptive controllers several controller architectures have been proposed in the literature. In this dissertation, we develop a new neuroadaptive control architecture for nonlinear uncertain dynamical systems. The proposed framework involves a novel controller architecture with additional terms in the update laws that are constructed using a moving window of the integrated system uncertainty. These terms can be used to identify the ideal system weights of the neural network as well as effectively suppress system uncertainty. Linear and nonlinear parameterizations of the system uncertainty are considered and state and output feedback neuroadaptive controllers are developed. Furthermore, we extend the developed framework to discrete-time dynamical systems. To illustrate the efficacy of the proposed approach we apply our results to an aircraft model with wing rock dynamics, a spacecraft model with unknown moment of inertia, and an unmanned combat aerial vehicle undergoing actuator failures, and compare our results with standard neuroadaptive control methods. Nonnegative systems are essential in capturing the behavior of a wide range of dynamical systems involving dynamic states whose values are nonnegative. A sub-class of nonnegative dynamical systems are compartmental systems. These systems are derived from mass and energy balance considerations and are comprised of homogeneous interconnected microscopic subsystems or compartments which exchange variable quantities of material via intercompartmental flow laws. In this dissertation, we develop direct adaptive and neuroadaptive control framework for stabilization, disturbance

  4. Shape control and compartmentalization in active colloidal cells

    PubMed Central

    Spellings, Matthew; Engel, Michael; Klotsa, Daphne; Sabrina, Syeda; Drews, Aaron M.; Nguyen, Nguyen H. P.; Bishop, Kyle J. M.; Glotzer, Sharon C.

    2015-01-01

    Small autonomous machines like biological cells or soft robots can convert energy input into control of function and form. It is desired that this behavior emerges spontaneously and can be easily switched over time. For this purpose we introduce an active matter system that is loosely inspired by biology and which we term an active colloidal cell. The active colloidal cell consists of a boundary and a fluid interior, both of which are built from identical rotating spinners whose activity creates convective flows. Similarly to biological cell motility, which is driven by cytoskeletal components spread throughout the entire volume of the cell, active colloidal cells are characterized by highly distributed energy conversion. We demonstrate that we can control the shape of the active colloidal cell and drive compartmentalization by varying the details of the boundary (hard vs. flexible) and the character of the spinners (passive vs. active). We report buckling of the boundary controlled by the pattern of boundary activity, as well as formation of core–shell and inverted Janus phase-separated configurations within the active cell interior. As the cell size is increased, the inverted Janus configuration spontaneously breaks its mirror symmetry. The result is a bubble–crescent configuration, which alternates between two degenerate states over time and exhibits collective migration of the fluid along the boundary. Our results are obtained using microscopic, non–momentum-conserving Langevin dynamics simulations and verified via a phase-field continuum model coupled to a Navier–Stokes equation. PMID:26253763

  5. Potassium Fluxes in Chlamydomonas reinhardtii (II. Compartmental Analysis).

    PubMed Central

    Malhotra, B.; Glass, ADM.

    1995-01-01

    42K+ and 86Rb+ were used to determine the subcellular distribution of potassium in Chlamydomonas reinhardtii by compartmental analysis. In both wild type and a mutant strain, three distinct compartments (referred to as I, II, and III) were apparent. Using 42K+, we found that these had half-lives for K+ exchange of 1.07 min, 12.8 min, and 2.9 h, respectively, in wild-type cells and 0.93 min, 14.7 min, and 9.8 h, respectively, for the mutants. Half-lives were not significantly different when 86Rb+ was used to trace K+. Compartments I and II probably correspond to the cell wall and cytoplasm, respectively. Based on the lack of a large central vacuole in Chlamydomonas, the effect of a dark pretreatment on the kinetic properties of compartment III and the similarity between the [K+] of compartment III and that of isolated chloroplasts, this slowly exchanging compartment was identified as the chloroplast. Growth of wild-type cells at 100 [mu]M (instead of 10 mM K+) caused no change of cytoplasmic [K+] but reduced chloroplast [K+] very substantially. The mutants failed to grow at 100 [mu]M K+. PMID:12228560

  6. Metabolic Compartmentation – A System Level Property of Muscle Cells

    PubMed Central

    Saks, Valdur; Beraud, Nathalie; Wallimann, Theo

    2008-01-01

    Problems of quantitative investigation of intracellular diffusion and compartmentation of metabolites are analyzed. Principal controversies in recently published analyses of these problems for the living cells are discussed. It is shown that the formal theoretical analysis of diffusion of metabolites based on Fick's equation and using fixed diffusion coefficients for diluted homogenous aqueous solutions, but applied for biological systems in vivo without any comparison with experimental results, may lead to misleading conclusions, which are contradictory to most biological observations. However, if the same theoretical methods are used for analysis of actual experimental data, the apparent diffusion constants obtained are orders of magnitude lower than those in diluted aqueous solutions. Thus, it can be concluded that local restrictions of diffusion of metabolites in a cell are a system-level properties caused by complex structural organization of the cells, macromolecular crowding, cytoskeletal networks and organization of metabolic pathways into multienzyme complexes and metabolons. This results in microcompartmentation of metabolites, their channeling between enzymes and in modular organization of cellular metabolic networks. The perspectives of further studies of these complex intracellular interactions in the framework of Systems Biology are discussed. PMID:19325782

  7. A development-based compartmentalization of the Drosophila central brain

    PubMed Central

    Pereanu, Wayne; Kumar, Abilasha; Jennett, Arnim; Reichert, Heinrich; Hartenstein, Volker

    2010-01-01

    The neuropile of the Drosophila brain is subdivided into anatomically discrete compartments. Compartments are rich in terminal neurite branching and synapses; they are the neuropile domains in which signal processing takes place. Compartment boundaries are defined by more or less dense layers of glial cells, as well as long neurite fascicles. These fascicles are formed during the larval period when the approximately 100 neuronal lineages that constitute the Drosophila central brain differentiate. Each lineage forms an axon tract with a characteristic trajectory in the neuropile; groups of spatially related tracts congregate into the brain fascicles that can be followed from the larva throughout metamorphosis into the adult stage. In this paper we provide a map of the adult brain compartments and the relevant fascicles defining compartmental boundaries. We have identified the neuronal lineages contributing to each fascicle, which allowed us to directly compare compartments of the larval and adult brain. Most adult compartments can be recognized already in the early larval brain where they form a “protomap” of the later adult compartments. Our analysis highlights the morphogenetic changes shaping the Drosophila brain; the data will be important for studies that link early acting genetic mechanisms to the adult neuronal structures and circuits controlled by these mechanisms. PMID:20533357

  8. Development-based compartmentalization of the Drosophila central brain.

    PubMed

    Pereanu, Wayne; Kumar, Abilasha; Jennett, Arnim; Reichert, Heinrich; Hartenstein, Volker

    2010-08-01

    The neuropile of the Drosophila brain is subdivided into anatomically discrete compartments. Compartments are rich in terminal neurite branching and synapses; they are the neuropile domains in which signal processing takes place. Compartment boundaries are defined by more or less dense layers of glial cells as well as long neurite fascicles. These fascicles are formed during the larval period, when the approximately 100 neuronal lineages that constitute the Drosophila central brain differentiate. Each lineage forms an axon tract with a characteristic trajectory in the neuropile; groups of spatially related tracts congregate into the brain fascicles that can be followed from the larva throughout metamorphosis into the adult stage. Here we provide a map of the adult brain compartments and the relevant fascicles defining compartmental boundaries. We have identified the neuronal lineages contributing to each fascicle, which allowed us to compare compartments of the larval and adult brain directly. Most adult compartments can be recognized already in the early larval brain, where they form a "protomap" of the later adult compartments. Our analysis highlights the morphogenetic changes shaping the Drosophila brain; the data will be important for studies that link early-acting genetic mechanisms to the adult neuronal structures and circuits controlled by these mechanisms. PMID:20533357

  9. Compartmentalized gene regulatory network of the pathogenic fungus Fusarium graminearum.

    PubMed

    Guo, Li; Zhao, Guoyi; Xu, Jin-Rong; Kistler, H Corby; Gao, Lixin; Ma, Li-Jun

    2016-07-01

    Head blight caused by Fusarium graminearum threatens world-wide wheat production, resulting in both yield loss and mycotoxin contamination. We reconstructed the global F. graminearum gene regulatory network (GRN) from a large collection of transcriptomic data using Bayesian network inference, a machine-learning algorithm. This GRN reveals connectivity between key regulators and their target genes. Focusing on key regulators, this network contains eight distinct but interwoven modules. Enriched for unique functions, such as cell cycle, DNA replication, transcription, translation and stress responses, each module exhibits distinct expression profiles. Evolutionarily, the F. graminearum genome can be divided into core regions shared with closely related species and variable regions harboring genes that are unique to F. graminearum and perform species-specific functions. Interestingly, the inferred top regulators regulate genes that are significantly enriched from the same genomic regions (P < 0.05), revealing a compartmentalized network structure that may reflect network rewiring related to specific adaptation of this plant pathogen. This first-ever reconstructed filamentous fungal GRN primes our understanding of pathogenicity at the systems biology level and provides enticing prospects for novel disease control strategies involving the targeting of master regulators in pathogens. The program can be used to construct GRNs of other plant pathogens. PMID:26990214

  10. Compartmentation of Malate in Relation to Ion Absorption in Beet

    PubMed Central

    Osmond, C. B.; Laties, George G.

    1969-01-01

    Malate in beet discs treated in different salt solutions was labeled by a 30 min pulse of 14CO2, and subsequent changes in specific activity were followed for several hr. In treatments which resulted in net acid synthesis in response to excess cation absorption, malate specific activity fell slowly after removal of 14CO2. In solutions where no net acid synthesis occurred, and from which cation and anion were absorbed equally, malate specific activity fell rapidly when 14CO2 was removed. The foregoing suggests that the net synthesis of organic acids in response to excess cation absorption leads to the removal of organic anions from cytoplasmic metabolic pools as counter-ions in salt transport to the vacuole. The latter hypothesis was further examined by direct measurement of the distribution of labeled malate between cytoplasm and vacuole using the wash-exchange method of compartmental analysis, previously described for inorganic ions. The method satisfied the criterion of exchange specificity necessary for this purpose. Much higher retention of label in the cytoplasm was observed in KCl solutions (no net synthesis) than in K2SO4 solutions (net synthesis) after 3 hr 14CO2 fixation and subsequent wash-exchange. The observed distribution is consistent with the rapid removal of organic anions to the vacuole during net acid synthesis. The significance of organic acid transport in relation to metabolism is discussed. PMID:16657035

  11. The R-Operon: A Model of Repetitive DNA-Organized Transcriptional Compartmentation of Eukaryotic Chromosomes for Coordinated Gene Expression

    PubMed Central

    Tang, Shao-Jun

    2016-01-01

    In eukaryotic genomes, it is essential to coordinate the activity of genes that function together to fulfill the same biological processes. Genomic organization likely plays a key role in coordinating transcription of different genes. However, little is known about how co-regulated genes are organized in the cell nucleus and how the chromosomal organization facilitates the co-regulation of different genes. I propose that eukaryotic genomes are organized into repeat assembly (RA)-based structural domains (“R-operons”) in the nuclear space. R-operons result from the interaction of homologous DNA repeats. In an R-operon, genes in different loci of the linear genome are brought into spatial vicinity and co-regulated by the same pool of transcription factors. This type of large-scale chromosomal organization may provide a mechanism for functional compartmentation of chromosomes to facilitate the transcriptional coordination of gene expression. PMID:27110825

  12. The R-Operon: A Model of Repetitive DNA-Organized Transcriptional Compartmentation of Eukaryotic Chromosomes for Coordinated Gene Expression.

    PubMed

    Tang, Shao-Jun

    2016-01-01

    In eukaryotic genomes, it is essential to coordinate the activity of genes that function together to fulfill the same biological processes. Genomic organization likely plays a key role in coordinating transcription of different genes. However, little is known about how co-regulated genes are organized in the cell nucleus and how the chromosomal organization facilitates the co-regulation of different genes. I propose that eukaryotic genomes are organized into repeat assembly (RA)-based structural domains ("R-operons") in the nuclear space. R-operons result from the interaction of homologous DNA repeats. In an R-operon, genes in different loci of the linear genome are brought into spatial vicinity and co-regulated by the same pool of transcription factors. This type of large-scale chromosomal organization may provide a mechanism for functional compartmentation of chromosomes to facilitate the transcriptional coordination of gene expression. PMID:27110825

  13. Compartmental Pharmacokinetic Analysis of Oral Amprenavir with Secondary Peaks▿

    PubMed Central

    Okusanya, Olanrewaju; Forrest, Alan; DiFrancesco, Robin; Bilic, Sanela; Rosenkranz, Susan; Para, Michael F.; Adams, Elizabeth; Yarasheski, Kevin E.; Reichman, Richard C.; Morse, Gene D.

    2007-01-01

    Amprenavir is a protease inhibitor that has been shown to have secondary peaks postulated to be due to enterohepatic recycling. We propose a model to describe the pharmacokinetics of amprenavir which accommodates the secondary peak(s). A total of 82 healthy human immunodeficiency virus (HIV)-seronegative subjects were administered a single 600-mg dose of amprenavir as part of adult AIDS Clinical Trials Group protocol A5043. Serial blood samples were obtained over 24 h. Samples were analyzed for amprenavir and fit to a compartmental model using ADAPT II software, with all relevant parameters conditional with respect to bioavailability. The model accommodated secondary peaks by incorporating clearance out of the central compartment with delayed instantaneous release back into the gut compartment. The data were weighted by the inverse of the estimated measurement error variance; model discrimination was determined using Akaike's Information Criteria. A total of 76 subjects were evaluable in the study analysis. The data were best fit by a two-compartment model, with 98.7% of the subjects demonstrating a secondary peak. Amprenavir had a mean total clearance of 1.163 liters/h/kg of body weight (0.7), a central volume of distribution of 1.208 liters/kg (0.8), a peripheral volume of distribution of 8.2 liters/kg (0.81), and distributional clearance of 0.04 liters/h/kg (0.81). The time to the secondary peak was 7.86 h (0.17), and clearance into a recycling compartment was 0.111 liters/kg/h (0.74). Amprenavir pharmacokinetics has been well described using a two-compartment model with clearance to a recycling compartment and release back into the gut. The nature of the secondary peaks may be an important consideration for the interpretation of amprenavir plasma concentrations during therapeutic drug monitoring. PMID:17283195

  14. In vivo compartmental analysis of leukocytes in mouse lungs.

    PubMed

    Patel, Brijesh V; Tatham, Kate C; Wilson, Michael R; O'Dea, Kieran P; Takata, Masao

    2015-10-01

    The lung has a unique structure consisting of three functionally different compartments (alveolar, interstitial, and vascular) situated in an extreme proximity. Current methods to localize lung leukocytes using bronchoalveolar lavage and/or lung perfusion have significant limitations for determination of location and phenotype of leukocytes. Here we present a novel method using in vivo antibody labeling to enable accurate compartmental localization/quantification and phenotyping of mouse lung leukocytes. Anesthetized C57BL/6 mice received combined in vivo intravenous and intratracheal labeling with fluorophore-conjugated anti-CD45 antibodies, and lung single-cell suspensions were analyzed by flow cytometry. The combined in vivo intravenous and intratracheal CD45 labeling enabled robust separation of the alveolar, interstitial, and vascular compartments of the lung. In naive mice, the alveolar compartment consisted predominantly of resident alveolar macrophages. The interstitial compartment, gated by events negative for both intratracheal and intravenous CD45 staining, showed two conventional dendritic cell populations, as well as a Ly6C(lo) monocyte population. Expression levels of MHCII on these interstitial monocytes were much higher than on the vascular Ly6C(lo) monocyte populations. In mice exposed to acid aspiration-induced lung injury, this protocol also clearly distinguished the three lung compartments showing the dynamic trafficking of neutrophils and exudative monocytes across the lung compartments during inflammation and resolution. This simple in vivo dual-labeling technique substantially increases the accuracy and depth of lung flow cytometric analysis, facilitates a more comprehensive examination of lung leukocyte pools, and enables the investigation of previously poorly defined "interstitial" leukocyte populations during models of inflammatory lung diseases. PMID:26254421

  15. Compartmentation and complexation of metals in hyperaccumulator plants

    PubMed Central

    Leitenmaier, Barbara; Küpper, Hendrik

    2013-01-01

    Hyperaccumulators are being intensely investigated. They are not only interesting in scientific context due to their “strange” behavior in terms of dealing with high concentrations of metals, but also because of their use in phytoremediation and phytomining, for which understanding the mechanisms of hyperaccumulation is crucial. Hyperaccumulators naturally use metal accumulation as a defense against herbivores and pathogens, and therefore deal with accumulated metals in very specific ways of complexation and compartmentation, different from non-hyperaccumulator plants and also non-hyperaccumulated metals. For example, in contrast to non-hyperaccumulators, in hyperaccumulators even the classical phytochelatin-inducing metal, cadmium, is predominantly not bound by such sulfur ligands, but only by weak oxygen ligands. This applies to all hyperaccumulated metals investigated so far, as well as hyperaccumulation of the metalloid arsenic. Stronger ligands, as they have been shown to complex metals in non-hyperaccumulators, are in hyperaccumulators used for transient binding during transport to the storage sites (e.g., nicotianamine) and possibly for export of Cu in Cd/Zn hyperaccumulators [metallothioneins (MTs)]. This confirmed that enhanced active metal transport, and not metal complexation, is the key mechanism of hyperaccumulation. Hyperaccumulators tolerate the high amount of accumulated heavy metals by sequestering them into vacuoles, usually in large storage cells of the epidermis. This is mediated by strongly elevated expression of specific transport proteins in various tissues from metal uptake in the shoots up to the storage sites in the leaf epidermis. However, this mechanism seems to be very metal specific. Non-hyperaccumulated metals in hyperaccumulators seem to be dealt with like in non-hyperaccumulator plants, i.e., detoxified by binding to strong ligands such as MTs. PMID:24065978

  16. The compartmentation of phosphorylated thiamine derivatives in cultured neuroblastoma cells.

    PubMed

    Bettendorff, L

    1994-05-26

    Thiamine transport in cultured neuroblastoma cells is mediated by a high-affinity carrier (KM = 40 nM). In contrast, the uptake of the more hydrophobic sulbutiamine (isobutyrylthiamine disulfide) is unsaturable and its initial transport rate is 20-times faster than for thiamine. In the cytoplasm, sulbutiamine is rapidly hydrolyzed and reduced to free thiamine, the overall process resulting in a rapid and concentrative thiamine accumulation. Incorporation of radioactivity from [14C]thiamine or [14C]sulbutiamine into intracellular thiamine diphosphate is slow in both cases. Despite the fact that the diphosphate is probably the direct precursor for both thiamine monophosphate and triphosphate, the specific radioactivity increased much faster for the latter two compounds than for thiamine diphosphate. This suggests the existence of two pools of thiamine diphosphate, the larger one having a very slow turnover (about 17 h); a much smaller, rapidly turning over pool would be the precursor of thiamine mono- and triphosphate. The turnover time for thiamine triphosphate could be estimated to be 1-2 h. When preloading the cells with [14C]sulbutiamine was followed by a chase with the same concentration of the unlabeled compound, the specific radioactivities of thiamine and thiamine monophosphate decreased exponentially as expected, but labeling of the diphosphate continued to increase slowly. Specific radioactivity of thiamine triphosphate increased first, but after 30 min it began to slowly decrease. These results show for the first time the existence of distinct thiamine diphosphate pools in the same homogeneous cell population. They also suggest a complex compartmentation of thiamine metabolism. PMID:8186267

  17. Efficient Vaccine Distribution Based on a Hybrid Compartmental Model

    PubMed Central

    Yu, Zhiwen; Liu, Jiming; Wang, Xiaowei; Zhu, Xianjun; Wang, Daxing; Han, Guoqiang

    2016-01-01

    To effectively and efficiently reduce the morbidity and mortality that may be caused by outbreaks of emerging infectious diseases, it is very important for public health agencies to make informed decisions for controlling the spread of the disease. Such decisions must incorporate various kinds of intervention strategies, such as vaccinations, school closures and border restrictions. Recently, researchers have paid increased attention to searching for effective vaccine distribution strategies for reducing the effects of pandemic outbreaks when resources are limited. Most of the existing research work has been focused on how to design an effective age-structured epidemic model and to select a suitable vaccine distribution strategy to prevent the propagation of an infectious virus. Models that evaluate age structure effects are common, but models that additionally evaluate geographical effects are less common. In this paper, we propose a new SEIR (susceptible—exposed—infectious šC recovered) model, named the hybrid SEIR-V model (HSEIR-V), which considers not only the dynamics of infection prevalence in several age-specific host populations, but also seeks to characterize the dynamics by which a virus spreads in various geographic districts. Several vaccination strategies such as different kinds of vaccine coverage, different vaccine releasing times and different vaccine deployment methods are incorporated into the HSEIR-V compartmental model. We also design four hybrid vaccination distribution strategies (based on population size, contact pattern matrix, infection rate and infectious risk) for controlling the spread of viral infections. Based on data from the 2009–2010 H1N1 influenza epidemic, we evaluate the effectiveness of our proposed HSEIR-V model and study the effects of different types of human behaviour in responding to epidemics. PMID:27233015

  18. Cyclic guanosine monophosphate compartmentation in rat cardiac myocytes

    PubMed Central

    Castro, Liliana R.V.; Verde, Ignacio; Cooper, Dermot M.; Fischmeister, Rodolphe

    2006-01-01

    Background Cyclic GMP is the common second messenger for the cardiovascular effects of nitric oxide (NO) and natriuretic peptides, such as ANP or BNP, which activate, respectively, the soluble and particulate form of guanylyl cyclase. Yet, natriuretic peptides and NO-donors exert different effects on cardiac and vascular smooth muscle function. We therefore tested whether these differences are due to an intracellular compartmentation of cGMP, and evaluated the role of phosphodiesterase (PDE) subtypes in this process. Methods and Results Subsarcolemmal cGMP signals were monitored in adult rat cardiomyocytes by expression of the rat olfactory CNG channel α subunit and recording of the associated cGMP-gated current (ICNG). ANP (10 nM) or BNP (10 nM) induced a clear activation of ICNG while NO-donors (SNAP, SNP, DEANO, SIN-1, spermine NO, all at 100 μM) had little effect. The ICNG current was strongly potentiated by non-selective PDE inhibition with IBMX (100 μM) and by the PDE2 inhibitors EHNA (10 μM) and Bay 60–7550 (50 nM). Surprisingly, sildenafil, a PDE5 inhibitor, produced a dose-dependent increase of ICNG activated by NO-donors but had no effect (at 100 nM) on the current elicited by ANP. Conclusions These results indicate that, in rat cardiomyocytes: i) the ‘particulate’ cGMP pool is readily accessible at the plasma membrane, while the ‘soluble’ pool is not; ii) PDE5 controls the ‘soluble’ but not the ‘particulate’ pool, whereas the latter is under the exclusive control of PDE2. Differential spatiotemporal distributions of cGMP may therefore contribute to the specific effects of natriuretic peptides and NO-donors on cardiac function. PMID:16651469

  19. Compartmental Intrathecal Radioimmunotherapy: Results for Treatment for Metastatic CNS Neuroblastoma

    PubMed Central

    Kramer, Kim; Kushner, Brian H.; Modak, Shakeel; Pandit-Taskar, Neeta; Smith-Jones, Peter; Zanzonico, Pat; Humm, John L.; Xu, Hong; Wolden, Suzanne L.; Souweidane, Mark M.; Larson, Steven M.; Cheung, Nai-Kong V.

    2012-01-01

    Innovation in the management of brain metastases is needed. We evaluated the addition of compartmental intrathecal antibody-based radioimmunotherapy (cRIT) in patients with recurrent metastatic central nervous system (CNS) neuroblastoma following surgery, craniospinal irradiation, and chemotherapy. 21 patients treated for recurrent neuroblastoma metastatic to the CNS received a cRIT-containing salvage regimen incorporating intrathecal 131I-monoclonal antibodies (MoAbs) targeting GD2 or B7H3 following surgery and radiation. Most patients also received outpatient craniospinal irradiation, 3F8/GMCSF immunotherapy, 13-cis-retinoic acid and oral temozolomide for systemic control. Seventeen of 21 cRIT-salvage patients are alive 7-74 months (median 33) since CNS relapse, with all 17 remaining free of CNS neuroblastoma. One patient died of infection at 22 months with no evidence of disease at autopsy, and one of lung and bone marrow metastases at 15 months, and one of progressive bone marrow disease at 30 months. The cRIT-salvage regimen was well tolerated, notable for myelosuppression minimized by stem cell support (n=5), and biochemical hypothyroidism (n=5). One patient with a 7-year history of metastatic neuroblastoma is in remission from MLL-associated secondary leukemia. This is significantly improved to published results with non-cRIT based where relapsed CNS NB has a median time to death of approximately 6 months. The cRIT-salvage regimen for CNS metastases was well tolerated by young patients, despite their prior history of intensive cytotoxic therapies. It has the potential to increase survival with better than expected quality of life. PMID:19890606

  20. Compartmentation and complexation of metals in hyperaccumulator plants.

    PubMed

    Leitenmaier, Barbara; Küpper, Hendrik

    2013-01-01

    Hyperaccumulators are being intensely investigated. They are not only interesting in scientific context due to their "strange" behavior in terms of dealing with high concentrations of metals, but also because of their use in phytoremediation and phytomining, for which understanding the mechanisms of hyperaccumulation is crucial. Hyperaccumulators naturally use metal accumulation as a defense against herbivores and pathogens, and therefore deal with accumulated metals in very specific ways of complexation and compartmentation, different from non-hyperaccumulator plants and also non-hyperaccumulated metals. For example, in contrast to non-hyperaccumulators, in hyperaccumulators even the classical phytochelatin-inducing metal, cadmium, is predominantly not bound by such sulfur ligands, but only by weak oxygen ligands. This applies to all hyperaccumulated metals investigated so far, as well as hyperaccumulation of the metalloid arsenic. Stronger ligands, as they have been shown to complex metals in non-hyperaccumulators, are in hyperaccumulators used for transient binding during transport to the storage sites (e.g., nicotianamine) and possibly for export of Cu in Cd/Zn hyperaccumulators [metallothioneins (MTs)]. This confirmed that enhanced active metal transport, and not metal complexation, is the key mechanism of hyperaccumulation. Hyperaccumulators tolerate the high amount of accumulated heavy metals by sequestering them into vacuoles, usually in large storage cells of the epidermis. This is mediated by strongly elevated expression of specific transport proteins in various tissues from metal uptake in the shoots up to the storage sites in the leaf epidermis. However, this mechanism seems to be very metal specific. Non-hyperaccumulated metals in hyperaccumulators seem to be dealt with like in non-hyperaccumulator plants, i.e., detoxified by binding to strong ligands such as MTs. PMID:24065978

  1. Functional morphometry demonstrates extraocular muscle compartmental contraction during vertical gaze changes.

    PubMed

    Clark, Robert A; Demer, Joseph L

    2016-01-01

    Anatomical studies demonstrate selective compartmental innervation of most human extraocular muscles (EOMs), suggesting the potential for differential compartmental control. This was supported by magnetic resonance imaging (MRI) demonstrating differential lateral rectus (LR) compartmental contraction during ocular counterrolling, differential medial rectus (MR) compartmental contraction during asymmetric convergence, and differential LR, inferior rectus (IR), and superior oblique (SO) compartmental contraction during vertical vergence. To ascertain possible differential compartmental EOM contraction during vertical ductions, surface coil MRI was performed over a range of target-controlled vertical gaze positions in 25 orbits of 13 normal volunteers. Cross-sectional areas and partial volumes of EOMs were analyzed in contiguous, quasi-coronal 2-mm image planes spanning origins to globe equator to determine morphometric features correlating best with contractility. Confirming and extending prior findings for horizontal EOMs during horizontal ductions, the percent change in posterior partial volume (PPV) of vertical EOMs from 8 to 14 mm posterior to the globe correlated best with vertical duction. EOMs were then divided into equal transverse compartments to evaluate the effect of vertical gaze on changes in PPV. Differential contractile changes were detected in the two compartments of the same EOM during infraduction for the IR medial vs. lateral (+4.4%, P = 0.03), LR inferior vs. superior (+4.0%, P = 0.0002), MR superior vs. inferior (-6.0%, P = 0.001), and SO lateral vs. medial (+9.7%, P = 0.007) compartments, with no differential contractile changes in the superior rectus. These findings suggest that differential compartmental activity occurs during normal vertical ductions. Thus all EOMs may contribute to cyclovertical actions. PMID:26538608

  2. In or out? Regulating nuclear transport.

    PubMed

    Hood, J K; Silver, P A

    1999-04-01

    The compartmentalization of proteins within the nucleus or cytoplasm of a eukaryotic cell offers opportunity for regulation of cell cycle progression and signalling pathways. Nuclear localization of proteins is determined by their ability to interact with specific nuclear import and export factors. In the past year, substrate phosphorylation has emerged as a common mechanism for controlling this interaction. PMID:10209150

  3. Compartmentalization of the foregut tube: developmental origins of the trachea and esophagus.

    PubMed

    Fausett, Sarah R; Klingensmith, John

    2012-01-01

    The mammalian trachea and esophagus share a common embryonic origin. They arise by compartmentalization of a single foregut tube, composed of foregut endoderm (FGE) and surrounding mesenchyme, around midgestation. Aberrant compartmentalization is thought to lead to relatively common human birth defects, such as esophageal atresia (EA) and tracheoesophageal fistula (EA/TEF), which can prevent or disrupt a newborn infant's ability to feed and breathe. Despite its relevance to human health, morphogenesis of the anterior foregut is still poorly understood. In this article, we provide a comprehensive review of trachea and esophagus formation from a common precursor, including the embryonic origin of the FGE, current models for foregut morphogenesis, relevant human birth defects, insights from rodent models, and the emerging picture of the mechanisms underlying normal and abnormal foregut compartmentalization. Recent research suggests that a number of intercellular signaling pathways and several intracellular effectors are essential for correct formation of the trachea and esophagus. Different types of defects in the formation of either ventral or dorsal foregut tissues can disrupt compartmentalization in rodent models. This implies that EA/TEF defects in humans may also arise by multiple mechanisms. Although our understanding of foregut compartmentalization is growing rapidly, it is still incomplete. Future research should focus on synthesizing detailed information gleaned from both human patients and rodent models to further our understanding of this enigmatic process. PMID:23801435

  4. Compartmentalization of cyclic nucleotide signaling: A question of when, where, and why?

    PubMed Central

    Arora, Kavisha; Sinha, Chandrima; Zhang, Weiqiang; Ren, Aixia; Moon, Chang Suk; Yarlagadda, Sunitha; Naren, Anjaparavanda P.

    2013-01-01

    Preciseness of cellular behavior depends upon how an extracellular cue mobilizes a correct orchestra of cellular messengers and effector proteins spatially and temporally. This concept, termed compartmentalization of cellular signaling, is now known to form the molecular basis of many aspects of cellular behavior in health and disease. The cyclic nucleotides cAMP and cGMP are ubiquitous cellular messengers that can be compartmentalized in three ways: first, by their physical containment; second, by formation of multiple protein signaling complexes; and third, by their selective depletion. Compartmentalized cyclic nucleotide signaling is a very prevalent response among all cell types. In order to understand how it becomes relevant to cellular behavior, it is important to know how it is executed in cells to regulate physiological responses and, also, how its execution or dysregulation can lead to a pathophysiological condition, which forms the current scope of the presented review. PMID:23604972

  5. Preventing Age-Related Decline of Gut Compartmentalization Limits Microbiota Dysbiosis and Extends Lifespan.

    PubMed

    Li, Hongjie; Qi, Yanyan; Jasper, Heinrich

    2016-02-10

    Compartmentalization of the gastrointestinal (GI) tract of metazoans is critical for health. GI compartments contain specific microbiota, and microbiota dysbiosis is associated with intestinal dysfunction. Dysbiosis develops in aging intestines, yet how this relates to changes in GI compartmentalization remains unclear. The Drosophila GI tract is an accessible model to address this question. Here we show that the stomach-like copper cell region (CCR) in the middle midgut controls distribution and composition of the microbiota. We find that chronic activation of JAK/Stat signaling in the aging gut induces a metaplasia of the gastric epithelium, CCR decline, and subsequent commensal dysbiosis and epithelial dysplasia along the GI tract. Accordingly, inhibition of JAK/Stat signaling in the CCR specifically prevents age-related metaplasia, commensal dysbiosis and functional decline in old guts, and extends lifespan. Our results establish a mechanism by which age-related chronic inflammation causes the decline of intestinal compartmentalization and microbiota dysbiosis, limiting lifespan. PMID:26867182

  6. Characterization of Golgi scaffold proteins and their roles in compartmentalizing cell signaling.

    PubMed

    Peng, Wenna; Lei, Qiang; Jiang, Zheng; Hu, Zhiping

    2014-08-01

    Subcellular compartmentalization has become an important theme in cell signaling. In particular, the Golgi apparatus (GA) plays a prominent role in compartmentalizing signaling cascades that originate at the plasma membrane or other organelles. To precisely regulate this process, cells have evolved a unique class of organizer proteins, termed "scaffold proteins". Sef, PAQR3, PAQR10 and PAQR11 are scaffold proteins that have recently been identified on the GA and are referred to as Golgi scaffolds. The major cell growth signaling pathways, such as Ras/MAPK, PI3K/AKT, insulin and VEGF (vascular endothelial growth factor), are tightly regulated spatially and temporally by these Golgi scaffolds to ensure a physiologically appropriate outcome. Here, we discuss the subcellular localization and characterization of the topology and functional domains of these Golgi scaffolds and summarize their roles in the compartmentalization of cell signaling. We also highlight the physiological and pathological roles of these Golgi scaffolds in tumorigenesis and developmental disorders. PMID:24337566

  7. Establishment and maintenance of compartmental boundaries: role of contractile actomyosin barriers.

    PubMed

    Monier, Bruno; Pélissier-Monier, Anne; Sanson, Bénédicte

    2011-06-01

    During animal development, tissues and organs are partitioned into compartments that do not intermix. This organizing principle is essential for correct tissue morphogenesis. Given that cell sorting defects during compartmentalization in humans are thought to cause malignant invasion and congenital defects such as cranio-fronto-nasal syndrome, identifying the molecular and cellular mechanisms that keep cells apart at boundaries between compartments is important. In both vertebrates and invertebrates, transcription factors and short-range signalling pathways, such as EPH/Ephrin, Hedgehog, or Notch signalling, govern compartmental cell sorting. However, the mechanisms that mediate cell sorting downstream of these factors have remained elusive for decades. Here, we review recent data gathered in Drosophila that suggest that the generation of cortical tensile forces at compartmental boundaries by the actomyosin cytoskeleton could be a general mechanism that inhibits cell mixing between compartments. PMID:21437644

  8. Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells

    PubMed Central

    Lewis, Caroline A.; Parker, Seth J.; Fiske, Brian P.; McCloskey, Douglas; Gui, Dan Y.; Green, Courtney R.; Vokes, Natalie I.; Feist, Adam M.; Heiden, Matthew G. Vander; Metallo, Christian M.

    2014-01-01

    Summary Eukaryotic cells compartmentalize biochemical processes in different organelles, often relying on metabolic cycles to shuttle reducing equivalents across intracellular membranes. NADPH serves as the electron carrier for the maintenance of redox homeostasis and reductive biosynthesis, with separate cytosolic and mitochondrial pools providing reducing power in each respective location. This cellular organization is critical for numerous functions but complicates analysis of metabolic pathways using available methods. Here we develop an approach to resolve NADP(H)-dependent pathways present within both the cytosol and the mitochondria. By tracing hydrogen in compartmentalized reactions that use NADPH as a cofactor, including the production of 2-hydroxyglutarate by mutant isocitrate dehydrogenase enzymes, we can observe metabolic pathway activity in these distinct cellular compartments. Using this system we determine the direction of serine/glycine interconversion within the mitochondria and cytosol, highlighting the ability of this approach to resolve compartmentalized reactions in intact cells. PMID:24882210

  9. Male genital tract compartmentalization of human immunodeficiency virus type 1 (HIV).

    PubMed

    Diem, Kurt; Nickle, David C; Motoshige, Alexis; Fox, Alan; Ross, Susan; Mullins, James I; Corey, Lawrence; Coombs, Robert W; Krieger, John N

    2008-04-01

    We present phylogenetic evidence supporting viral compartmentalization between the blood (peripheral blood mononuclear cells or plasma) and multiple genitourinary sites in HIV-infected men. Four of the five subjects evaluated demonstrated compartmentalization of viral sequences between urogenital tract specimens (tissue or fluid) and at least one blood category. HIV sequence migration from blood to urogenital tract was detected in four of five men, with migration from urogenital tract to blood in the fifth, and cross migration between both compartments noted in one man. These observations add 5 additional cases to the 27 total reported cases in which male urogenital tract compartmentalization has been studied, investigate surgical samples/specimens that have not been evaluated previously, and provide further evidence for restricted flow of HIV between the blood and the genital tract. As such, our study findings are important for understanding the long-term response to antiretroviral therapy, the design of vaccines, and the sexual transmission of HIV. PMID:18426336

  10. A Computational Modeling and Simulation Approach to Investigate Mechanisms of Subcellular cAMP Compartmentation.

    PubMed

    Yang, Pei-Chi; Boras, Britton W; Jeng, Mao-Tsuen; Docken, Steffen S; Lewis, Timothy J; McCulloch, Andrew D; Harvey, Robert D; Clancy, Colleen E

    2016-07-01

    Subcellular compartmentation of the ubiquitous second messenger cAMP has been widely proposed as a mechanism to explain unique receptor-dependent functional responses. How exactly compartmentation is achieved, however, has remained a mystery for more than 40 years. In this study, we developed computational and mathematical models to represent a subcellular sarcomeric space in a cardiac myocyte with varying detail. We then used these models to predict the contributions of various mechanisms that establish subcellular cAMP microdomains. We used the models to test the hypothesis that phosphodiesterases act as functional barriers to diffusion, creating discrete cAMP signaling domains. We also used the models to predict the effect of a range of experimentally measured diffusion rates on cAMP compartmentation. Finally, we modeled the anatomical structures in a cardiac myocyte diad, to predict the effects of anatomical diffusion barriers on cAMP compartmentation. When we incorporated experimentally informed model parameters to reconstruct an in silico subcellular sarcomeric space with spatially distinct cAMP production sites linked to caveloar domains, the models predict that under realistic conditions phosphodiesterases alone were insufficient to generate significant cAMP gradients. This prediction persisted even when combined with slow cAMP diffusion. When we additionally considered the effects of anatomic barriers to diffusion that are expected in the cardiac myocyte dyadic space, cAMP compartmentation did occur, but only when diffusion was slow. Our model simulations suggest that additional mechanisms likely contribute to cAMP gradients occurring in submicroscopic domains. The difference between the physiological and pathological effects resulting from the production of cAMP may be a function of appropriate compartmentation of cAMP signaling. Therefore, understanding the contribution of factors that are responsible for coordinating the spatial and temporal

  11. A Computational Modeling and Simulation Approach to Investigate Mechanisms of Subcellular cAMP Compartmentation

    PubMed Central

    Yang, Pei-Chi; Boras, Britton W.; Jeng, Mao-Tsuen; Lewis, Timothy J.; McCulloch, Andrew D.; Harvey, Robert D.; Clancy, Colleen E.

    2016-01-01

    Subcellular compartmentation of the ubiquitous second messenger cAMP has been widely proposed as a mechanism to explain unique receptor-dependent functional responses. How exactly compartmentation is achieved, however, has remained a mystery for more than 40 years. In this study, we developed computational and mathematical models to represent a subcellular sarcomeric space in a cardiac myocyte with varying detail. We then used these models to predict the contributions of various mechanisms that establish subcellular cAMP microdomains. We used the models to test the hypothesis that phosphodiesterases act as functional barriers to diffusion, creating discrete cAMP signaling domains. We also used the models to predict the effect of a range of experimentally measured diffusion rates on cAMP compartmentation. Finally, we modeled the anatomical structures in a cardiac myocyte diad, to predict the effects of anatomical diffusion barriers on cAMP compartmentation. When we incorporated experimentally informed model parameters to reconstruct an in silico subcellular sarcomeric space with spatially distinct cAMP production sites linked to caveloar domains, the models predict that under realistic conditions phosphodiesterases alone were insufficient to generate significant cAMP gradients. This prediction persisted even when combined with slow cAMP diffusion. When we additionally considered the effects of anatomic barriers to diffusion that are expected in the cardiac myocyte dyadic space, cAMP compartmentation did occur, but only when diffusion was slow. Our model simulations suggest that additional mechanisms likely contribute to cAMP gradients occurring in submicroscopic domains. The difference between the physiological and pathological effects resulting from the production of cAMP may be a function of appropriate compartmentation of cAMP signaling. Therefore, understanding the contribution of factors that are responsible for coordinating the spatial and temporal

  12. Multiple sampling and discriminatory fingerprinting reveals clonally complex and compartmentalized infections by M. bovis in cattle.

    PubMed

    Navarro, Yurena; Romero, Beatriz; Copano, María Francisca; Bouza, Emilio; Domínguez, Lucas; de Juan, Lucía; García-de-Viedma, Darío

    2015-01-30

    The combination of new genotyping tools and a more exhaustive sampling policy in the analysis of infection by Mycobacterium tuberculosis has shown that infection by this pathogen is more complex than initially expected. Mixed infections, coexistence of clonal variants from a parental strain, and compartmentalized infections are all different modalities of this clonal complexity. Until recently, genotyping of Mycobacterium bovis in animal populations was based on spoligotyping and analysis of a single isolate per infection; therefore, clonal complexity is probably underdetected. We used multiple sampling combined with highly discriminatory MIRU-VNTR to study compartmentalized infections by M. bovis in a low-tuberculosis prevalence setting. We spoligotyped the M. bovis isolates from two or more anatomic locations sampled from 55 animals on 39 independent farms. Compartmentalized infections, with two different strains infecting independent lymph nodes in the same animal, were found in six cases (10.9%). MIRU-VNTR analysis confirmed that the compartmentalization was strict and that only one strain was present in each infected node. MIRU-VNTR analysis of additional infected animals on one of the farms confirmed that the compartmentalized infection was a consequence of superinfection, since the two strains were independently infecting other animals. This same analysis revealed the emergence of a microevolved clonal variant in one of the lymph nodes of the compartmentalized animal. Clonal complexity must also be taken into consideration in M. bovis infection, even in low-prevalence settings, and analyses must be adapted to detect it and increase the accuracy of molecular epidemiology studies. PMID:25439651

  13. Compartmentation of cAMP signalling in cardiomyocytes in health and disease.

    PubMed

    Perera, R K; Nikolaev, V O

    2013-04-01

    3',5'-cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger critically involved in the regulation of heart function. It has been shown to act in discrete subcellular signalling compartments formed by differentially localized receptors, phosphodiesterases and protein kinases. Cardiac diseases such as hypertrophy or heart failure are associated with structural and functional remodelling of these microdomains which leads to changes in cAMP compartmentation. In this review, we will discuss recent key findings which provided new insights into cAMP compartmentation in cardiomyocytes with a particular focus on its alterations in heart disease. PMID:23383621

  14. 21 CFR 888.3535 - Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .../polymer porous-coated uncemented prosthesis. 888.3535 Section 888.3535 Food and Drugs FOOD AND DRUG... Devices § 888.3535 Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis. (a) Identification. A knee joint femorotibial (uni-compartmental) metal/polymer...

  15. 21 CFR 888.3535 - Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .../polymer porous-coated uncemented prosthesis. 888.3535 Section 888.3535 Food and Drugs FOOD AND DRUG... Devices § 888.3535 Knee joint femorotibial (uni-compartmental) metal/polymer porous-coated uncemented prosthesis. (a) Identification. A knee joint femorotibial (uni-compartmental) metal/polymer...

  16. Beyond Compartmentalization: A Relational Approach towards Agency and Vulnerability of Young Migrants

    ERIC Educational Resources Information Center

    Huijsmans, Roy

    2012-01-01

    Based on fieldwork material from Lao People's Democratic Republic, this paper introduces an analytical framework that transcends compartmentalized approaches towards migration involving young people. The notions of fluid and institutionalized forms of migration illuminate key differences and commonalities in the relational fabric underpinning…

  17. Origin of reservoir compartmentalization in Lower Ordovician Karstic Dolostones, Ellenburger Group, West Texas

    SciTech Connect

    Kerans, C.

    1988-01-01

    Ellenburger Group reservoirs constitute a major play in the Permian basin of west Texas, with over 1.4 billion bbl cumulative production through 1985. These reservoirs typically have been developed by assuming homogeneous fracture-related pore system. Examination of core, log, and production data demonstrates that most Ellenburger reservoirs are characterized by pronounced vertical and lateral heterogeneities created by post-Ellenburger karst development. Vertical reservoir compartmentalization in the Ellenburger evolved from development of a laterally extensive cave system between 100 and 300 ft beneath the original land surface. Caves were filled by relatively impermeable siliciclastics from the overlying Simpson Group, effectively isolating permeable cave-roof breccias (uppermost Ellenburger) from collapse breccias deposited on cave floors prior to shale infill. Lateral compartmentalization of Ellenburger reservoirs originated by localized collapse of the cave system both during karst formation and after burial. In the Shafter Lake field, lateral compartmentalization is the result of a 200-ft vertical collapse during deposition of Simpson Group sands. Abrupt lateral discontinuities in the Big Lake and Glasco fields may represent similar collapse-related features, such as are spectacularly displayed in Ellenburger-equivalent outcrops of the Franklin Mountains. An estimated 750 million bbl of remaining mobile oil, in addition to conventional reserves, occurs in this mature but complexly compartmentalized play. Considering this paleokarst model will aid in further exploitation of Ellenburger reservoirs.

  18. Analysis of a compartmental model of amyloid beta production, irreversible loss and exchange in humans

    PubMed Central

    Elbert, Donald L.; Patterson, Bruce W.; Bateman, Randall J.

    2014-01-01

    Amyloid beta (Aβ) peptides, and in particular Aβ42, are found in senile plaques associated with Alzheimer's disease. A compartmental model of Aβ production, exchange and irreversible loss was recently developed to explain the kinetics of isotope-labeling of Aβ peptides collected in cerebrospinal fluid (CSF) following infusion of stable isotope-labeled leucine in humans. The compartmental model allowed calculation of the rates of production, irreversible loss (or turnover) and short-term exchange of Aβ peptides. Exchange of Aβ42 was particularly pronounced in amyloid plaque-bearing participants. In the current work, we describe in much greater detail the characteristics of the compartmental model to two distinct audiences: physician-scientists and biokineticists. For physician-scientists, we describe through examples the types of questions the model can and cannot answer, as well as correct some misunderstandings of previous kinetic analyses applied to this type of isotope labeling data. For biokineticists, we perform a system identifiability analysis and a sensitivity analysis of the kinetic model to explore the global and local properties of the model. Combined, these analyses motivate simplifications from a more comprehensive physiological model to the final model that was previously presented. The analyses clearly demonstrate that the current dataset and compartmental model allow determination with confidence a single ‘turnover’ parameter, a single ‘exchange’ parameter and a single ‘delay’ parameter. When combined with CSF concentration data for the Aβ peptides, production rates may also be obtained. PMID:25497960

  19. Technology Solutions Case Study: Field Testing of Compartmentalization Methods for Multifamily Construction

    SciTech Connect

    2015-01-01

    Fire-resistance rated (or area separation) wall assemblies present a great difficulty in air sealing/compartmentalization, particularly in townhouse construction. To address this challenge, Building Science Corporation partnered with builder K. Hovnanian Homes to determine whether taping exterior sheathing details improves air sealing in townhouse and multifamily construction, and to better understand air leakage pathways.

  20. Analysis of a compartmental model of amyloid beta production, irreversible loss and exchange in humans.

    PubMed

    Elbert, Donald L; Patterson, Bruce W; Bateman, Randall J

    2015-03-01

    Amyloid beta (Aβ) peptides, and in particular Aβ42, are found in senile plaques associated with Alzheimer's disease. A compartmental model of Aβ production, exchange and irreversible loss was recently developed to explain the kinetics of isotope-labeling of Aβ peptides collected in cerebrospinal fluid (CSF) following infusion of stable isotope-labeled leucine in humans. The compartmental model allowed calculation of the rates of production, irreversible loss (or turnover) and short-term exchange of Aβ peptides. Exchange of Aβ42 was particularly pronounced in amyloid plaque-bearing participants. In the current work, we describe in much greater detail the characteristics of the compartmental model to two distinct audiences: physician-scientists and biokineticists. For physician-scientists, we describe through examples the types of questions the model can and cannot answer, as well as correct some misunderstandings of previous kinetic analyses applied to this type of isotope labeling data. For biokineticists, we perform a system identifiability analysis and a sensitivity analysis of the kinetic model to explore the global and local properties of the model. Combined, these analyses motivate simplifications from a more comprehensive physiological model to the final model that was previously presented. The analyses clearly demonstrate that the current dataset and compartmental model allow determination with confidence a single 'turnover' parameter, a single 'exchange' parameter and a single 'delay' parameter. When combined with CSF concentration data for the Aβ peptides, production rates may also be obtained. PMID:25497960

  1. A-kinase anchoring proteins: cAMP compartmentalization in neurodegenerative and obstructive pulmonary diseases

    PubMed Central

    Poppinga, W J; Muñoz-Llancao, P; González-Billault, C; Schmidt, M

    2014-01-01

    The universal second messenger cAMP is generated upon stimulation of Gs protein-coupled receptors, such as the β2-adreneoceptor, and leads to the activation of PKA, the major cAMP effector protein. PKA oscillates between an on and off state and thereby regulates a plethora of distinct biological responses. The broad activation pattern of PKA and its contribution to several distinct cellular functions lead to the introduction of the concept of compartmentalization of cAMP. A-kinase anchoring proteins (AKAPs) are of central importance due to their unique ability to directly and/or indirectly interact with proteins that either determine the cellular content of cAMP, such as β2-adrenoceptors, ACs and PDEs, or are regulated by cAMP such as the exchange protein directly activated by cAMP. We report on lessons learned from neurons indicating that maintenance of cAMP compartmentalization by AKAP5 is linked to neurotransmission, learning and memory. Disturbance of cAMP compartments seem to be linked to neurodegenerative disease including Alzheimer's disease. We translate this knowledge to compartmentalized cAMP signalling in the lung. Next to AKAP5, we focus here on AKAP12 and Ezrin (AKAP78). These topics will be highlighted in the context of the development of novel pharmacological interventions to tackle AKAP-dependent compartmentalization. PMID:25132049

  2. SYNCHROTRON X-RAY ABSORPTION-EDGE COMPUTED MICROTOMOGRAPHY IMAGING OF THALLIUM COMPARTMENTALIZATION IN IBERIS INTERMEDIA

    EPA Science Inventory

    Thallium (TI) is an extremely toxic metal which, due to its similarities to K, is readily taken up by plants. Thallium is efficiently hyperaccumulated in Iberis intermedia as TI(I). Distribution and compartmentalization of TI in I. intermedia is highes...

  3. Analysis of a non-structural gene reveals evidence of possible hepatitis C virus (HCV) compartmentalization

    PubMed Central

    Blackard, Jason T.; Ma, Gang; Welge, Jeffrey A.; Martin, Christina M.; Sherman, Kenneth E.; Taylor, Lynn E.; Mayer, Kenneth H.; Jamieson, Denise J.

    2011-01-01

    Viral diversity is a hallmark of hepatitis C virus (HCV) infection; however, only limited data are available regarding HCV variability in extrahepatic sites, and none have systematically compared diversity in non-structural and structural genomic regions. Therefore, HCV diversity in the NS5B and envelope 1 (E1) hypervariable region 1 (HVR1) genes was evaluated in matched sera and peripheral blood mononuclear cells (PBMCs) obtained from 13 HCV-infected women. Multiple clonal sequences were compared to evaluate quasispecies diversity and viral compartmentalization in PBMCs. Genetic distances were higher for E1/HVR1 compared to NS5B in both the sera and PBMCs (p = 0.0511 and p = 0.0284). Genetic distances were higher in serum NS5B compared to PBMC NS5B (p = 0.0003); however, they were not different when comparing E1/HVR1 in sera to PBMCs. By phylogenetic analysis of NS5B, evidence of possible PBMC compartmentalization was observed for 1 woman, while statistical methods were consistent with PBMC compartmentalization for 6 women. Evidence of compartmentalization within a non-structural genomic region may suggest that viral adaptation to a unique extracellular microenvironment(s) may be required for efficient replication and could contribute to HCV persistence. PMID:22170544

  4. Compartmentalization of Calcium Extrusion Mechanisms in the Outer and Inner Segments of Photoreceptors

    PubMed Central

    Copenhagen, David R.

    2010-01-01

    Summary Differential localization of calcium channel subtypes in divergent regions of individual neurons strongly suggests that calcium signaling and regulation could be compartmentalized. Region-specific expression of calcium extrusion transporters would serve also to partition calcium regulation within single cells. Little is known about selective localization of the calcium extrusion transporters, nor has compartmentalized calcium regulation within single neurons been studied in detail. Sensory neurons provide an experimentally tractable preparation to investigate this functional compartmentalization. We studied calcium regulation in the outer segment (OS) and inner segment/synaptic terminal (IS/ST) regions of rods and cones. We report these areas can function as separate compartments. Moreover, ionic, pharmacological, and immunolocalization results show that a Ca-ATPase, but not the Na+/K+, Ca2+ exchanger found in the OSs, extrudes calcium from the IS/ST region. The compartmentalization of calcium regulation in the photoreceptor outer and inner segments implies that transduction and synaptic signaling can be independently controlled. Similar separation of calcium-dependent functions is likely to apply in many types of neuron. PMID:9697868

  5. An actomyosin-based barrier inhibits cell mixing at compartmental boundaries in Drosophila embryos.

    PubMed

    Monier, Bruno; Pélissier-Monier, Anne; Brand, Andrea H; Sanson, Bénédicte

    2010-01-01

    Partitioning tissues into compartments that do not intermix is essential for the correct morphogenesis of animal embryos and organs. Several hypotheses have been proposed to explain compartmental cell sorting, mainly differential adhesion, but also regulation of the cytoskeleton or of cell proliferation. Nevertheless, the molecular and cellular mechanisms that keep cells apart at boundaries remain unclear. Here we demonstrate, in early Drosophila melanogaster embryos, that actomyosin-based barriers stop cells from invading neighbouring compartments. Our analysis shows that cells can transiently invade neighbouring compartments, especially when they divide, but are then pushed back into their compartment of origin. Actomyosin cytoskeletal components are enriched at compartmental boundaries, forming cable-like structures when the epidermis is mitotically active. When MyoII (non-muscle myosin II) function is inhibited, including locally at the cable by chromophore-assisted laser inactivation (CALI), in live embryos, dividing cells are no longer pushed back, leading to compartmental cell mixing. We propose that local regulation of actomyosin contractibility, rather than differential adhesion, is the primary mechanism sorting cells at compartmental boundaries. PMID:19966783

  6. Self-structure and self-esteem stability: the hidden vulnerability of compartmentalization.

    PubMed

    Zeigler-Hill, Virgil; Showers, Carolin J

    2007-02-01

    The present studies examined the association between self-concept structure and stability of self-esteem. In two daily diary studies, evaluative integration (organizing positively and negatively valenced self-beliefs into the same self-aspects) was associated with more stable self-esteem than evaluative compartmentalization (organizing positively and negatively valenced self-beliefs into separate self-aspects) among individuals with generally high self-esteem. Moreover, analyses of self-esteem reactivity confirmed that the sensitivity of state self-esteem to daily events was greater for compartmentalized individuals than for individuals with relatively integrative self-concept structures. Compartmentalization also was associated with greater sensitivity to experiences of social rejection in the laboratory, consistent with the view that integration affords greater stability of self-evaluations. These results suggest that some of the benefits believed to be associated with compartmentalization (such as high self-esteem) may have hidden costs that have not previously been considered. PMID:17259577

  7. Jesús and María in the jungle: an essay on possibility and constraint in the third-shift third space

    NASA Astrophysics Data System (ADS)

    Richardson Bruna, Katherine

    2009-03-01

    One hundred years ago, Upton Sinclair, in The Jungle, exposed the deplorable working conditions of eastern European immigrants in the meatpacking houses of Chicago. The backdrop of this article is the new Jungle of the 21st century—the hog plants of the rural Midwest. Here I speak to the lives of the Mexican workers they employ, and, more specifically, the science-learning experiences and aspirations of third-shifters, Jesús and María. I use these students' stories as an opportunity to examine the take-up, in education, of the concept of hybridity, and, more particularly, to interrogate what I have come to regard as the "third space fetish." My principle argument is that Bhabha's understanding of liberatory Third Space has been distorted, in education, through teacher-centered and power-neutral multicultural discourse. I call for a more robust approach to hybridity in science education research, guided by the lessons of possibility and constraint contained in Jesús' and María's third-shift third space lives.

  8. Syntheses, crystal structures, and water adsorption behaviors of jungle-gym-type porous coordination polymers containing nitro moieties

    SciTech Connect

    Uemura, Kazuhiro; Onishi, Fumiaki; Yamasaki, Yukari; Kita, Hidetoshi

    2009-10-15

    NO{sub 2} containing dicarboxylate bridging ligands, nitroterephthalate (bdc-NO{sub 2}) and 2,5-dinitroterephthalate (bdc-(NO{sub 2}){sub 2}), afford porous coordination polymers, {l_brace}[Zn{sub 2}(bdc-NO{sub 2}){sub 2}(dabco)].solvents{r_brace}{sub n} (2 contains solvents) and {l_brace}[Zn{sub 2}(bdc-(NO{sub 2}){sub 2}){sub 2}(dabco)].solvents{r_brace}{sub n} (3 contains solvents). Both compounds form jungle-gym-type regularities, where a 2D square grid composed of dinuclear Zn{sub 2} units and dicarboxylate ligands is bridged by dabco molecules to extend the 2D layers into a 3D structure. In 2 contains solvents and 3 contains solvents, a rectangle pore surrounded by eight Zn{sub 2} corners contains two and four NO{sub 2} moieties, respectively. Thermal gravimetry (TG) and X-ray powder diffraction (XRPD) measurements reveal that both compounds maintain the frameworks regularities without guest molecules and with solvents such as MeOH, EtOH, i-PrOH, and Me{sub 2}CO. Adsorption measurements reveal that dried 2 and 3 adsorb H{sub 2}O molecules to be {l_brace}[Zn{sub 2}(bdc-NO{sub 2}){sub 2}(dabco)].4H{sub 2}O{r_brace}{sub n} (2 contains 4H{sub 2}O) and {l_brace}[Zn{sub 2}(bdc-(NO{sub 2}){sub 2}){sub 2}(dabco)].6H{sub 2}O{r_brace}{sub n} (3 contains 6H{sub 2}O), showing the pore hydrophilicity enhancement caused by NO{sub 2} group introduction. - Graphical abstract: Two hydrophilic porous coordination polymers, [Zn{sub 2}(bdc-NO{sub 2}){sub 2}(dabco)]{sub n} (2, bdc-NO{sub 2}=nitroterephthalate, dabco=1,4-diazabicyclo[2.2.2]octane) and [Zn{sub 2}(bdc-(NO{sub 2}){sub 2}){sub 2}(dabco)]{sub n} (3, bdc-(NO{sub 2}){sub 2}=2,5-dinitroterephthalate), have been synthesized and characterized by single X-ray analyses, thermal gravimetry, and adsorption measurements.

  9. Surveillance of nuclear pore complex assembly by ESCRT-III/Vps4

    PubMed Central

    Webster, Brant M.; Colombi, Paolo; Jäger, Jens; Lusk, C. Patrick

    2014-01-01

    SUMMARY The maintenance of nuclear compartmentalization by the nuclear envelope and nuclear pore complexes (NPCs) is essential for cell function; loss of compartmentalization is associated with cancers, laminopathies and aging. We uncovered a pathway that surveils NPC assembly intermediates to promote the formation of functional NPCs. Surveillance is mediated by Heh2, a member of the LEM (Lap2-emerin-MAN1) family of integral inner nuclear membrane proteins, which binds to an early NPC assembly intermediate, but not to mature NPCs. Heh2 recruits the Endosomal Sorting Complex Required for Transport (ESCRT) – III subunit Snf7 and the AAA-ATPase Vps4 to destabilize and clear defective NPC assembly intermediates. When surveillance or clearance is compromised, malformed NPCs accumulate in a Storage of Improperly assembled Nuclear Pore Complexes compartment, or SINC. The SINC is retained in old mothers to prevent loss of daughter lifespan, highlighting a continuum of mechanisms to ensure nuclear compartmentalization. PMID:25303532

  10. The relationship of natural and artificial maturation: Evidence for pressure compartmentalization, and for coal as a source of petroleum

    SciTech Connect

    MacGowan, D.B.; Britton, D.R.; Surdam, R.C. . Dept. of Geology and Geophysics)

    1992-01-01

    In the Greater Green River Basin (GRB), the Almond Fm. is an important reservoir, having yielded cumulative production of 100 MBO and 0.7 TCFG through 1986. A regional study of Almond Fm. shales and coals in wells from the northwestern to the southeastern GRB was undertaken. Core samples from the Almond Fm. were subjected to: anhydrous pyrolysis, total organic carbon, vitrinite reflectance, and nuclear magnetic resonance analyses. The Almond appears to be a moderate to rich source rock, and in the oil window over the depth range of sampling (4,500 - 14,500 ft.). Additionally, a series of hydrous pyrolysis experiments were conducted on Almond coal samples at temperatures of 290 to 360 C. The organic-geochemical analyses performed on the core samples were also performed on these coal samples. These experiments show that Almond coal may be a significant source of liquid hydrocarbons (27 mg oil/g coal) as well as a prolific source of natural gas (7.52 x 10[sup [minus]6] moles natural gas/g coal). Gas production from tight gas sands accounts for about 20% of gas production from the Almond; almost all of this production is from overpressured reservoirs that produce little or not water, conditions characteristic of compartmentalized, abnormally-pressured sandstones. Comparison of maturation trends observed in the well core data with the hydrous pyrolysis data suggest that this mechanism also may operate in the Almond Fm. in the GRB.

  11. Use of a simulated annealing algorithm to fit compartmental models with an application to fractal pharmacokinetics.

    PubMed

    Marsh, Rebeccah E; Riauka, Terence A; McQuarrie, Steve A

    2007-01-01

    Increasingly, fractals are being incorporated into pharmacokinetic models to describe transport and chemical kinetic processes occurring in confined and heterogeneous spaces. However, fractal compartmental models lead to differential equations with power-law time-dependent kinetic rate coefficients that currently are not accommodated by common commercial software programs. This paper describes a parameter optimization method for fitting individual pharmacokinetic curves based on a simulated annealing (SA) algorithm, which always converged towards the global minimum and was independent of the initial parameter values and parameter bounds. In a comparison using a classical compartmental model, similar fits by the Gauss-Newton and Nelder-Mead simplex algorithms required stringent initial estimates and ranges for the model parameters. The SA algorithm is ideal for fitting a wide variety of pharmacokinetic models to clinical data, especially those for which there is weak prior knowledge of the parameter values, such as the fractal models. PMID:17706176

  12. Self-Assembly and Compartmentalization of Nanozymes in Mesoporous Silica-Based Nanoreactors.

    PubMed

    Huang, Yanyan; Lin, Youhui; Ran, Xiang; Ren, Jinsong; Qu, Xiaogang

    2016-04-11

    Herein, to mimic complex natural system, polyelectrolyte multilayer (PEM)-coated mesoporous silica nanoreactors were used to compartmentalize two different artificial enzymes. PEMs coated on the surface of mesoporous silica could serve as a permeable membrane to control the flow of molecules. When assembling hemin on the surface of mesoporous silica, the hemin-based mesoporous silica system possessed remarkable peroxidase-like activity, especially at physiological pH, and could be recycled more easily than traditional graphene-hemin nanocompounds. The hope is that these new findings may pave the way for exploring novel nanoreactors to achieve compartmentalization of nanozymes and applying artificial cascade catalytic systems to mimic cell organelles or important biochemical transformations. PMID:26934043

  13. A note on the compartmental analysis and related issues in laser Doppler flowmetry.

    PubMed

    Zhong, J; Nilsson, G E; Salerud, G E; Seifalian, A M

    1998-04-01

    Compartmental analysis (CA) in laser Doppler flowmetry (LDF) means deciphering the nutritional and thermoregulating flows from the measured perfusion flux. Based on the new theories proposed in [1] and [2], the CA is formulated here as an optimal approximation without directly involving the geometric information of the vessel network. It is seen that this approximation approach could also solve the biological zero (BZ) problem simultaneously, therefore, it actually provides a systematic solution to the BZ problem without estimating the BZ flux experimentally. In addition, the BZ problem with compartmental differences is reformulated, and the condition under which multiple compartments can be treated as a single one is investigated. The result, together with some computer simulations, showed that the theory in [2] is still an easy and useful approximation in practice. This note serves as an useful supplement to [1] and [2] and may help to solve and clarify some critical problems in LDF. PMID:9556971

  14. Structurally controlled and aligned tight gas reservoir compartmentalization in the San Juan and Piceance Basins

    SciTech Connect

    Decker, A.D.; Kuuskraa, V.A.; Klawitter, A.L.

    1995-10-01

    Recurrent basement faulting is the primary controlling mechanism for aligning and compartmentalizing upper Cretaceous aged tight gas reservoirs of the San Juan and Piceance Basins. Northwest trending structural lineaments that formed in conjunction with the Uncompahgre Highlands have profoundly influenced sedimentation trends and created boundaries for gas migration; sealing and compartmentalizing sedimentary packages in both basins. Fractures which formed over the structural lineaments provide permeability pathways which allowing gas recovery from otherwise tight gas reservoirs. Structural alignments and associated reservoir compartments have been accurately targeted by integrating advanced remote sensing imagery, high resolution aeromagnetics, seismic interpretation, stratigraphic mapping and dynamic structural modelling. This unifying methodology is a powerful tool for exploration geologists and is also a systematic approach to tight gas resource assessment in frontier basins.

  15. Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols.

    PubMed

    Avalos, José L; Fink, Gerald R; Stephanopoulos, Gregory

    2013-04-01

    Efforts to improve the production of a compound of interest in Saccharomyces cerevisiae have mainly involved engineering or overexpression of cytoplasmic enzymes. We show that targeting metabolic pathways to mitochondria can increase production compared with overexpression of the enzymes involved in the same pathways in the cytoplasm. Compartmentalization of the Ehrlich pathway into mitochondria increased isobutanol production by 260%, whereas overexpression of the same pathway in the cytoplasm only improved yields by 10%, compared with a strain overproducing enzymes involved in only the first three steps of the biosynthetic pathway. Subcellular fractionation of engineered strains revealed that targeting the enzymes of the Ehrlich pathway to the mitochondria achieves greater local enzyme concentrations. Other benefits of compartmentalization may include increased availability of intermediates, removing the need to transport intermediates out of the mitochondrion and reducing the loss of intermediates to competing pathways. PMID:23417095

  16. The MATCHIT Automaton: Exploiting Compartmentalization for the Synthesis of Branched Polymers

    PubMed Central

    Weyland, Mathias S.; Fellermann, Harold; Hadorn, Maik; Sorek, Daniel; Lancet, Doron; Rasmussen, Steen; Füchslin, Rudolf M.

    2013-01-01

    We propose an automaton, a theoretical framework that demonstrates how to improve the yield of the synthesis of branched chemical polymer reactions. This is achieved by separating substeps of the path of synthesis into compartments. We use chemical containers (chemtainers) to carry the substances through a sequence of fixed successive compartments. We describe the automaton in mathematical terms and show how it can be configured automatically in order to synthesize a given branched polymer target. The algorithm we present finds an optimal path of synthesis in linear time. We discuss how the automaton models compartmentalized structures found in cells, such as the endoplasmic reticulum and the Golgi apparatus, and we show how this compartmentalization can be exploited for the synthesis of branched polymers such as oligosaccharides. Lastly, we show examples of artificial branched polymers and discuss how the automaton can be configured to synthesize them with maximal yield. PMID:24489601

  17. Bioinspired genotype–phenotype linkages: mimicking cellular compartmentalization for the engineering of functional proteins

    PubMed Central

    van Vliet, Liisa D.; Colin, Pierre-Yves; Hollfelder, Florian

    2015-01-01

    The idea of compartmentalization of genotype and phenotype in cells is key for enabling Darwinian evolution. This contribution describes bioinspired systems that use in vitro compartments—water-in-oil droplets and gel-shell beads—for the directed evolution of functional proteins. Technologies based on these principles promise to provide easier access to protein-based therapeutics, reagents for processes involving enzyme catalysis, parts for synthetic biology and materials with biological components. PMID:26464791

  18. Simulation of Drug Uptake in a Two Compartmental Fractional Model for a Biological System.

    PubMed

    Petráš, Ivo; Magin, Richard L

    2011-12-01

    This paper presents a very effective numerical method for the solution of the two-compartmental pharmacokinetic model for oral drug administration. This model consists of a set of two fractional order differential equations which connect the two compartments. The first compartment represents the gut while the second compartment corresponds to the drug concentration in the target tissue. For ease of computation, the numerical solution is also created as a Matlab function. PMID:21822359

  19. GM130 is required for compartmental organization of dendritic Golgi outposts

    PubMed Central

    Zhou, Wei; Chang, Jin; Wang, Xin; Savelieff, Masha G.; Zhao, Yinyin; Ke, Shanshan; Ye, Bing

    2014-01-01

    SUMMARY Golgi complexes (Golgi) play important roles in the development and function of neurons [1–3]. Not only are Golgi present in the neuronal soma (somal Golgi) but they also exist in the dendrites as Golgi outposts [4–7]. Previous studies have shown that Golgi outposts serve as local microtubule organizing centers [8] and secretory stations in dendrites [6, 9]. It is unknown whether the structure and function of Golgi outposts differ from those of somal Golgi. Here we show in Drosophila that, unlike somal Golgi, the biochemically distinct cis, medial, and trans compartments of Golgi are often disconnected in dendrites in vivo. The Golgi structural protein GM130 is responsible for connecting distinct Golgi compartments in soma and dendritic branch points, and specific distribution of GM130 determines the compartmental organization of dendritic Golgi in dendritic shafts. We further show that compartmental organization regulates the role of Golgi in acentrosomal microtubule growth in dendrites and in dendritic branching. Our study provides insights into the structure and function of dendritic Golgi outposts as well as the regulation of compartmental organization of Golgi in general. PMID:24835455

  20. Compartmentalization Approaches in Soft Matter Science: From Nanoreactor Development to Organelle Mimics.

    PubMed

    Schoonen, Lise; van Hest, Jan C M

    2016-02-10

    Compartmentalization is an essential feature found in living cells to ensure that biological processes occur without being affected by undesired external influences. Over the years many scientists have designed self-assembled soft matter structures that mimic these natural catalytic compartments. The rationale behind this research is threefold. First of all, compartmentalization leads to the creation of a secluded environment for the catalytic species, which solves compatibility issues and which can improve catalyst efficiency and selectivity. Secondly, nano- and micro-compartments are constructed with the aim to obtain microenvironments that more closely mimic the cellular architecture. These biomimetic platforms are used to attain a better understanding of how cellular processes are executed. Thirdly, natural design rules are applied to create biomolecular assemblies with unusual functionality, which for example are used as artificial organelles. Here, recent developments will be discussed regarding these compartmentalized catalytic systems, with a selected number of illustrative examples to demonstrate which strategies have been followed, and to show to what extent the ambitious goals of this field of science have been reached. The focus here is on the field of soft matter science, covering the wide spectrum from polymeric assemblies to protein nanocages. PMID:26509964

  1. Intracellular compartmentation of ions in salt adapted tobacco cells. [Nicotiana tabacum L

    SciTech Connect

    Binzel, M.L.; Hess, F.D.; Bressan, R.A.; Hasegawa, P.M. )

    1988-02-01

    Na{sup +} and Cl{sup {minus}} are the principal solutes utilized for osmotic adjustment in cells of Nicotiana tabacum L. var Wisconsin 38 (tobacco) adapted to NaCl, accumulating to levels of 472 and 386 millimolar, respectively, in cells adapted to 428 millimolar NaCl. X-ray microanalysis of unetched frozen-hydrated cells adapted to salt indicated that Na{sup +} and Cl{sup {minus}} were compartmentalized in the vacuole, at concentrations of 780 and 624 millimolar, respectively, while cytoplasmic concentrations of the ions were maintained at 96 millimolar. The morphometric differences which existed between unadapted and salt adapted cells, (cytoplasmic volume of 22 and 45% of the cell, respectively), facilitated containment of the excited volume of the x-ray signal in the cytoplasm of the adapted cells. Confirmation of ion compartmentation in salt adapted cells was obtained based on kinetic analyses of {sup 22}Na{sup +} and {sup 36}Cl{sup {minus}} efflux from cells in steady state. These data provide evidence that ion compartmentation is a component of salt adaptation of glycophyte cells.

  2. Compartmentalization of incompatible reagents within Pickering emulsion droplets for one-pot cascade reactions.

    PubMed

    Yang, Hengquan; Fu, Luman; Wei, Lijuan; Liang, Jifen; Binks, Bernard P

    2015-01-28

    It is a dream that future synthetic chemistry can mimic living systems to process multistep cascade reactions in a one-pot fashion. One of the key challenges is the mutual destruction of incompatible or opposing reagents, for example, acid and base, oxidants and reductants. A conceptually novel strategy is developed here to address this challenge. This strategy is based on a layered Pickering emulsion system, which is obtained through lamination of Pickering emulsions. In this working Pickering emulsion, the dispersed phase can separately compartmentalize the incompatible reagents to avoid their mutual destruction, while the continuous phase allows other reagent molecules to diffuse freely to access the compartmentalized reagents for chemical reactions. The compartmentalization effects and molecular transport ability of the Pickering emulsion were investigated. The deacetalization-reduction, deacetalization-Knoevenagel, deacetalization-Henry and diazotization-iodization cascade reactions demonstrate well the versatility and flexibility of our strategy in processing the one-pot cascade reactions involving mutually destructive reagents. PMID:25603470

  3. The mechanics of cellular compartmentalization as a model for tumor spreading

    NASA Astrophysics Data System (ADS)

    Fritsch, Anatol; Pawlizak, Steve; Zink, Mareike; Kaes, Josef A.

    2012-02-01

    Based on a recently developed surgical method of Michael H"ockel, which makes use of cellular confinement to compartments in the human body, we study the mechanics of the process of cell segregation. Compartmentalization is a fundamental process of cellular organization and occurs during embryonic development. A simple model system can demonstrate the process of compartmentalization: When two populations of suspended cells are mixed, this mixture will eventually segregate into two phases, whereas mixtures of the same cell type will not. In the 1960s, Malcolm S. Steinberg formulated the so-called differential adhesion hypothesis which explains the segregation in the model system and the process of compartmentalization by differences in surface tension and adhesiveness of the interacting cells. We are interested in to which extend the same physical principles affect tumor growth and spreading between compartments. For our studies, we use healthy and cancerous breast cell lines of different malignancy as well as primary cells from human cervix carcinoma. We apply a set of techniques to study their mechanical properties and interactions. The Optical Stretcher is used for whole cell rheology, while Cell-cell-adhesion forces are directly measured with a modified AFM. In combination with 3D segregation experiments in droplet cultures we try to clarify the role of surface tension in tumor spreading.

  4. Verification of Compartmental Epidemiological Models using Metamorphic Testing, Model Checking and Visual Analytics

    SciTech Connect

    Ramanathan, Arvind; Steed, Chad A; Pullum, Laura L

    2012-01-01

    Compartmental models in epidemiology are widely used as a means to model disease spread mechanisms and understand how one can best control the disease in case an outbreak of a widespread epidemic occurs. However, a significant challenge within the community is in the development of approaches that can be used to rigorously verify and validate these models. In this paper, we present an approach to rigorously examine and verify the behavioral properties of compartmen- tal epidemiological models under several common modeling scenarios including birth/death rates and multi-host/pathogen species. Using metamorphic testing, a novel visualization tool and model checking, we build a workflow that provides insights into the functionality of compartmental epidemiological models. Our initial results indicate that metamorphic testing can be used to verify the implementation of these models and provide insights into special conditions where these mathematical models may fail. The visualization front-end allows the end-user to scan through a variety of parameters commonly used in these models to elucidate the conditions under which an epidemic can occur. Further, specifying these models using a process algebra allows one to automatically construct behavioral properties that can be rigorously verified using model checking. Taken together, our approach allows for detecting implementation errors as well as handling conditions under which compartmental epidemiological models may fail to provide insights into disease spread dynamics.

  5. Analysis of the Compartmentalized Metabolome – A Validation of the Non-Aqueous Fractionation Technique

    PubMed Central

    Klie, Sebastian; Krueger, Stephan; Krall, Leonard; Giavalisco, Patrick; Flügge, Ulf-Ingo; Willmitzer, Lothar; Steinhauser, Dirk

    2011-01-01

    With the development of high-throughput metabolic technologies, a plethora of primary and secondary compounds have been detected in the plant cell. However, there are still major gaps in our understanding of the plant metabolome. This is especially true with regards to the compartmental localization of these identified metabolites. Non-aqueous fractionation (NAF) is a powerful technique for the determination of subcellular metabolite distributions in eukaryotic cells, and it has become the method of choice to analyze the distribution of a large number of metabolites concurrently. However, the NAF technique produces a continuous gradient of metabolite distributions, not discrete assignments. Resolution of these distributions requires computational analyses based on marker molecules to resolve compartmental localizations. In this article we focus on expanding the computational analysis of data derived from NAF. Along with an experimental workflow, we describe the critical steps in NAF experiments and how computational approaches can aid in assessing the quality and robustness of the derived data. For this, we have developed and provide a new version (v1.2) of the BestFit command line tool for calculation and evaluation of subcellular metabolite distributions. Furthermore, using both simulated and experimental data we show the influence on estimated subcellular distributions by modulating important parameters, such as the number of fractions taken or which marker molecule is selected. Finally, we discuss caveats and benefits of NAF analysis in the context of the compartmentalized metabolome. PMID:22645541

  6. Diminished viral replication and compartmentalization of hepatitis C virus in hepatocellular carcinoma tissue.

    PubMed

    Harouaka, Djamila; Engle, Ronald E; Wollenberg, Kurt; Diaz, Giacomo; Tice, Ashley B; Zamboni, Fausto; Govindarajan, Sugantha; Alter, Harvey; Kleiner, David E; Farci, Patrizia

    2016-02-01

    Analysis of hepatitis C virus (HCV) replication and quasispecies distribution within the tumor of patients with HCV-associated hepatocellular carcinoma (HCC) can provide insight into the role of HCV in hepatocarcinogenesis and, conversely, the effect of HCC on the HCV lifecycle. In a comprehensive study of serum and multiple liver specimens from patients with HCC who underwent liver transplantation, we found a sharp and significant decrease in HCV RNA in the tumor compared with surrounding nontumorous tissues, but found no differences in multiple areas of control non-HCC cirrhotic livers. Diminished HCV replication was not associated with changes in miR-122 expression. HCV genetic diversity was significantly higher in livers containing HCC compared with control non-HCC cirrhotic livers. Tracking of individual variants demonstrated changes in the viral population between tumorous and nontumorous areas, the extent of which correlated with the decline in HCV RNA, suggesting HCV compartmentalization within the tumor. In contrast, compartmentalization was not observed between nontumorous areas and serum, or in controls between different areas of the cirrhotic liver or between liver and serum. Our findings indicate that HCV replication within the tumor is restricted and compartmentalized, suggesting segregation of specific viral variants in malignant hepatocytes. PMID:26787866

  7. Multi-scale hierarchical approach for parametric mapping: assessment on multi-compartmental models.

    PubMed

    Rizzo, G; Turkheimer, F E; Bertoldo, A

    2013-02-15

    This paper investigates a new hierarchical method to apply basis function to mono- and multi-compartmental models (Hierarchical-Basis Function Method, H-BFM) at a voxel level. This method identifies the parameters of the compartmental model in its nonlinearized version, integrating information derived at the region of interest (ROI) level by segmenting the cerebral volume based on anatomical definition or functional clustering. We present the results obtained by using a two tissue-four rate constant model with two different tracers ([(11)C]FLB457 and [carbonyl-(11)C]WAY100635), one of the most complex models used in receptor studies, especially at the voxel level. H-BFM is robust and its application on both [(11)C]FLB457 and [carbonyl-(11)C]WAY100635 allows accurate and precise parameter estimates, good quality parametric maps and a low percentage of voxels out of physiological bound (<8%). The computational time depends on the number of basis functions selected and can be compatible with clinical use (~6h for a single subject analysis). The novel method is a robust approach for PET quantification by using compartmental modeling at the voxel level. In particular, different from other proposed approaches, this method can also be used when the linearization of the model is not appropriate. We expect that applying it to clinical data will generate reliable parametric maps. PMID:23220428

  8. Compartmental models: theory and practice using the SAAM II software system.

    PubMed

    Cobelli, C; Foster, D M

    1998-01-01

    Understanding in vivo the functioning of metabolic systems at the whole-body or regional level requires one to make some assumptions on how the system works and to describe them mathematically, that is, to postulate a model of the system. Models of systems can have different characteristics depending on the properties of the system and the database available for their study; they can be deterministic or stochastic, dynamic or static, with lumped or distributed parameters. Metabolic systems are dynamic systems and we focus here on the most widely used class of dynamic (differential equation) models: compartmental models. This is a class of models for which the governing law is conservation of mass. It is a very attractive class to users because it formalizes physical intuition in a simple and reasonable way. Compartmental models are lumped parameter models, in that the events in the system are described by a finite number of changing variables, and are thus described by ordinary differential equations. While stochastic compartment models can also be defined, we discuss here the deterministic versions--those that can work with exact relationships between model variables. These are the models most widely used in discussions of endocrinology and metabolism. In this chapter, we will discuss the theory of compartmental models, and then discuss how the SAAM II software system, a system designed specifically to aid in the development and testing of multicompartmental models, can be used. PMID:9781383

  9. Diminished viral replication and compartmentalization of hepatitis C virus in hepatocellular carcinoma tissue

    PubMed Central

    Harouaka, Djamila; Engle, Ronald E.; Wollenberg, Kurt; Diaz, Giacomo; Tice, Ashley B.; Zamboni, Fausto; Govindarajan, Sugantha; Alter, Harvey; Kleiner, David E.; Farci, Patrizia

    2016-01-01

    Analysis of hepatitis C virus (HCV) replication and quasispecies distribution within the tumor of patients with HCV-associated hepatocellular carcinoma (HCC) can provide insight into the role of HCV in hepatocarcinogenesis and, conversely, the effect of HCC on the HCV lifecycle. In a comprehensive study of serum and multiple liver specimens from patients with HCC who underwent liver transplantation, we found a sharp and significant decrease in HCV RNA in the tumor compared with surrounding nontumorous tissues, but found no differences in multiple areas of control non-HCC cirrhotic livers. Diminished HCV replication was not associated with changes in miR-122 expression. HCV genetic diversity was significantly higher in livers containing HCC compared with control non-HCC cirrhotic livers. Tracking of individual variants demonstrated changes in the viral population between tumorous and nontumorous areas, the extent of which correlated with the decline in HCV RNA, suggesting HCV compartmentalization within the tumor. In contrast, compartmentalization was not observed between nontumorous areas and serum, or in controls between different areas of the cirrhotic liver or between liver and serum. Our findings indicate that HCV replication within the tumor is restricted and compartmentalized, suggesting segregation of specific viral variants in malignant hepatocytes. PMID:26787866

  10. Combined Noninvasive Imaging and Modeling Approaches Reveal Metabolic Compartmentation in the Barley Endosperm[W][OA

    PubMed Central

    Rolletschek, Hardy; Melkus, Gerd; Grafahrend-Belau, Eva; Fuchs, Johannes; Heinzel, Nicolas; Schreiber, Falk; Jakob, Peter M.; Borisjuk, Ljudmilla

    2011-01-01

    The starchy endosperm of cereals is a priori taken as a metabolically uniform tissue. By applying a noninvasive assay based on 13C/1H-magnetic resonance imaging (MRI) to barley (Hordeum vulgare) grains, we uncovered metabolic compartmentation in the endosperm. 13C-Suc feeding during grain filling showed that the primary site of Ala synthesis was the central region of the endosperm, the part of the caryopsis experiencing the highest level of hypoxia. Region-specific metabolism in the endosperm was characterized by flux balance analysis (FBA) and metabolite profiling. FBA predicts that in the central region of the endosperm, the tricarboxylic acid cycle shifts to a noncyclic mode, accompanied by elevated glycolytic flux and the accumulation of Ala. The metabolic compartmentation within the endosperm is advantageous for the grain's carbon and energy economy, with a prominent role being played by Ala aminotransferase. An investigation of caryopses with a genetically perturbed tissue pattern demonstrated that Ala accumulation is a consequence of oxygen status, rather than being either tissue specific or dependent on the supply of Suc. Hence the 13C-Ala gradient can be used as an in vivo marker for hypoxia. The combination of MRI and metabolic modeling offers opportunities for the noninvasive analysis of metabolic compartmentation in plants. PMID:21856793

  11. Nuclear Neighborhoods and Gene Expression

    PubMed Central

    Zhao, Rui; Bodnar, Megan S.; Spector, David L.

    2009-01-01

    Summary The eukaryotic nucleus is a highly compartmentalized and dynamic environment. Chromosome territories are arranged non-randomly within the nucleus and numerous studies have indicated that a gene’s position in the nucleus can impact its transcriptional activity. Here, we focus on recent advances in our understanding of the influence of specific nuclear neighborhoods on gene expression or repression. Nuclear neighborhoods associated with transcriptional repression include the inner nuclear membrane/nuclear lamina and peri-nucleolar chromatin, whereas neighborhoods surrounding the nuclear pore complex, PML nuclear bodies, and nuclear speckles seem to be transcriptionally permissive. While nuclear position appears to play an important role in gene expression, it is likely to be only one piece of a flexible puzzle that incorporates numerous parameters. We are still at a very early, yet exciting stage in our journey toward deciphering the mechanism(s) that govern the permissiveness of gene expression/repression within different nuclear neighborhoods. PMID:19339170

  12. Near-infrared light responsive multi-compartmental hydrogel particles synthesized through droplets assembly induced by superhydrophobic surface.

    PubMed

    Luo, Rongcong; Cao, Ye; Shi, Peng; Chen, Chia-Hung

    2014-12-10

    Light-responsive hydrogel particles with multi-compartmental structure are useful for applications in microreactors, drug delivery and tissue engineering because of their remotely-triggerable releasing ability and combinational functionalities. The current methods of synthesizing multi-compartmental hydrogel particles typically involve multi-step interrupted gelation of polysaccharides or complicated microfluidic procedures with limited throughput. In this study, a two-step sequential gelation process is developed to produce agarose/alginate double network multi-compartmental hydrogel particles using droplets assemblies induced by superhydrophobic surface as templates. The agarose/alginate double network multi-compartmental hydrogel particles can be formed with diverse hierarchical structures showing combinational functionalities. The synthesized hydrogel particles, when loaded with polypyrrole (PPy) nanoparticles that act as photothermal nanotransducers, are demonstrated to function as near-infrared (NIR) light triggerable and deformation-free hydrogel materials. Periodic NIR laser switching is applied to stimulate these hydrogel particles, and pulsatile release profiles are collected. Compared with massive reagents released from single-compartmental hydrogel particles, more regulated release profiles of the multi-compartmental hydrogel particles are observed. PMID:25059988

  13. A molecular analysis of the patterns of genetic diversity in local chickens from western Algeria in comparison with commercial lines and wild jungle fowls.

    PubMed

    Mahammi, F Z; Gaouar, S B S; Laloë, D; Faugeras, R; Tabet-Aoul, N; Rognon, X; Tixier-Boichard, M; Saidi-Mehtar, N

    2016-02-01

    The objectives of this study were to characterize the genetic variability of village chickens from three agro-ecological regions of western Algeria: coastal (CT), inland plains (IP) and highlands (HL), to reveal any underlying population structure, and to evaluate potential genetic introgression from commercial lines into local populations. A set of 233 chickens was genotyped with a panel of 23 microsatellite markers. Geographical coordinates were individually recorded. Eight reference populations were included in the study to investigate potential gene flow: four highly selected commercial pure lines and four lines of French slow-growing chickens. Two populations of wild red jungle fowls were also genotyped to compare the range of diversity between domestic and wild fowls. A genetic diversity analysis was conducted both within and between populations. Multivariate redundancy analyses were performed to assess the relative influence of geographical location among Algerian ecotypes. The results showed a high genetic variability within the Algerian population, with 184 alleles and a mean number of 8.09 alleles per locus. The values of heterozygosity (He and Ho) ranged from 0.55 to 0.62 in Algerian ecotypes and were smaller than values found in Jungle fowl populations and higher than values found in commercial populations. Although the structuring analysis of genotypes did not reveal clear subpopulations within Algerian ecotypes, the supervised approach using geographical data showed a significant (p < 0.01) differentiation between the three ecotypes which was mainly due to altitude. Thus, the genetic diversity of Algerian ecotypes may be under the influence of two factors with contradictory effects: the geographical location and climatic conditions may induce some differentiation, whereas the high level of exchanges and gene flow may suppress it. Evidence of gene flow between commercial and Algerian local populations was observed, which may be due to unrecorded

  14. The Peru Cervical Cancer Screening Study (PERCAPS): the design and implementation of a mother/daughter screen, treat, and vaccinate program in the Peruvian jungle.

    PubMed

    Abuelo, Carolina E; Levinson, Kimberly L; Salmeron, Jorge; Sologuren, Carlos Vallejos; Fernandez, Maria Jose Vallejos; Belinson, Jerome L

    2014-06-01

    Peru struggles to prevent cervical cancer (CC). In the jungle, prevention programs suffer from significant barriers although technology exists to detect CC precursors. This study used community based participatory research (CBPR) methods to overcome barriers. The objective was to evaluate the utility of CBPR techniques in a mother-child screen/treat and vaccinate program for CC prevention in the Peruvian jungle. The CC prevention program used self-sampling for human papillomavirus (HPV) for screening, cryotherapy for treatment and the HPV vaccine Gardasil for vaccination. Community health leaders (HL) from around Iquitos participated in a two half day educational course. The HLs then decided how to implement interventions in their villages or urban sectors. The success of the program was measured by: (1) ability of the HLs to determine an implementation plan, (2) proper use of research forms, (3) participation and retention rates, and (4) participants' satisfaction. HLs successfully registered 320 women at soup kitchens, schools, and health posts. Screening, treatment, and vaccination were successfully carried out using forms for registration, consent, and results with minimum error. In the screen/treat intervention 100% of participants gave an HPV sample and 99.7% reported high satisfaction; 81% of HPV + women were treated, and 57% returned for 6-month followup. Vaccine intervention: 98% of girls received the 1st vaccine, 88% of those received the 2nd, and 65% the 3rd. CBPR techniques successfully helped implement a screen/treat and vaccinate CC prevention program around Iquitos, Peru. These techniques may be appropriate for large-scale preventive health-care interventions. PMID:24276617

  15. The Learning Theory Jungle

    ERIC Educational Resources Information Center

    Minter, Robert L.

    2011-01-01

    This article addresses the myriad of pedagogical and andragogical issues facing university educators in the student learning process. It briefly explores the proliferation of learning theories in an attempt to develop awareness among faculty who teach at the university/college levels that not all theories of learning apply to the adult learner. In…

  16. [A checklists' jungle].

    PubMed

    Boermeester, Marja A

    2012-01-01

    The steps of any procedure can be summed up in a checklist. The question is whether that is efficient and effective. A patient safety checklist must be more than a collection of tick boxes. An effective safety checklist in healthcare should cover only complex procedures with an inherent risk hazard, being performed in a complex environment, where memory and situational awareness of a team can be channelled by using a checklist. It is counterproductive to have separate checklists, each covering an isolated part of a process. The use of technical equipment by medical personnel is prone to error. Knowledge of how to use that piece of equipment is essential; medical specialists have their own responsibility in terms of possession of adequate skills. Maintenance and function checks are key to safe use. Checks of equipment or devices prior to surgery should be done as part of a generic perioperative checklist. PMID:22894811

  17. Development and testing of a compartmentalized reaction network model for redox zones in contaminated aquifers

    USGS Publications Warehouse

    Abrams, R.H.; Loague, K.; Kent, D.B.

    1998-01-01

    The work reported here is the first part of a larger effort focused on efficient numerical simulation of redox zone development in contaminated aquifers. The sequential use of various electron acceptors, which is governed by the energy yield of each reaction, gives rise to redox zones. The large difference in energy yields between the various redox reactions leads to systems of equations that are extremely ill-conditioned. These equations are very difficult to solve, especially in the context of coupled fluid flow, solute transport, and geochemical simulations. We have developed a general, rational method to solve such systems where we focus on the dominant reactions, compartmentalizing them in a manner that is analogous to the redox zones that are often observed in the field. The compartmentalized approach allows us to easily solve a complex geochemical system as a function of time and energy yield, laying the foundation for our ongoing work in which we couple the reaction network, for the development of redox zones, to a model of subsurface fluid flow and solute transport. Our method (1) solves the numerical system without evoking a redox parameter, (2) improves the numerical stability of redox systems by choosing which compartment and thus which reaction network to use based upon the concentration ratios of key constituents, (3) simulates the development of redox zones as a function of time without the use of inhibition factors or switching functions, and (4) can reduce the number of transport equations that need to be solved in space and time. We show through the use of various model performance evaluation statistics that the appropriate compartment choice under different geochemical conditions leads to numerical solutions without significant error. The compartmentalized approach described here facilitates the next phase of this effort where we couple the redox zone reaction network to models of fluid flow and solute transport.

  18. Regulation of NAD+ metabolism, signaling and compartmentalization in the yeast Saccharomyces cerevisiae.

    PubMed

    Kato, Michiko; Lin, Su-Ju

    2014-11-01

    Pyridine nucleotides are essential coenzymes in many cellular redox reactions in all living systems. In addition to functioning as a redox carrier, NAD(+) is also a required co-substrate for the conserved sirtuin deacetylases. Sirtuins regulate transcription, genome maintenance and metabolism and function as molecular links between cells and their environment. Maintaining NAD(+) homeostasis is essential for proper cellular function and aberrant NAD(+) metabolism has been implicated in a number of metabolic- and age-associated diseases. Recently, NAD(+) metabolism has been linked to the phosphate-responsive signaling pathway (PHO pathway) in the budding yeast Saccharomyces cerevisiae. Activation of the PHO pathway is associated with the production and mobilization of the NAD(+) metabolite nicotinamide riboside (NR), which is mediated in part by PHO-regulated nucleotidases. Cross-regulation between NAD(+) metabolism and the PHO pathway has also been reported; however, detailed mechanisms remain to be elucidated. The PHO pathway also appears to modulate the activities of common downstream effectors of multiple nutrient-sensing pathways (Ras-PKA, TOR, Sch9/AKT). These signaling pathways were suggested to play a role in calorie restriction-mediated beneficial effects, which have also been linked to Sir2 function and NAD(+) metabolism. Here, we discuss the interactions of these pathways and their potential roles in regulating NAD(+) metabolism. In eukaryotic cells, intracellular compartmentalization facilitates the regulation of enzymatic functions and also concentrates or sequesters specific metabolites. Various NAD(+)-mediated cellular functions such as mitochondrial oxidative phosphorylation are compartmentalized. Therefore, we also discuss several key players functioning in mitochondrial, cytosolic and vacuolar compartmentalization of NAD(+) intermediates, and their potential roles in NAD(+) homeostasis. To date, it remains unclear how NAD(+) and NAD(+) intermediates

  19. Effects of cholesterol depletion on compartmentalized cAMP responses in adult cardiac myocytes

    PubMed Central

    Agarwal, Shailesh R.; MacDougall, David A.; Tyser, Richard; Pugh, Sara D.; Calaghan, Sarah C.; Harvey, Robert D.

    2011-01-01

    β1-Adrenergic receptors (β1ARs) and E-type prostaglandin receptors (EPRs) both produce compartmentalized cAMP responses in cardiac myocytes. The role of cholesterol-dependent lipid rafts in producing these compartmentalized responses was investigated in adult rat ventricular myocytes. β1ARs were found in lipid raft and non-lipid raft containing membrane fractions, while EPRs were only found in non-lipid raft fractions. Furthermore, β1AR activation enhanced the L-type Ca2+ current, intracellular Ca2+ transient, and myocyte shortening, while EPR activation had no effect, consistent with the idea that these functional responses are regulated by cAMP produced by receptors found in lipid raft domains. Using methyl-β-cyclodextrin to disrupt lipid rafts by depleting membrane cholesterol did not eliminate compartmentalized behavior, but it did selectively alter specific receptor-mediated responses. Cholesterol depletion enhanced the sensitivity of functional responses produced by β1ARs without having any effect on EPR activation. Changes in cAMP activity were also measured in intact cells using two different FRET-based biosensors: a type II PKA-based probe to monitor cAMP in subcellular compartments that include microdomains associated with caveolar lipid rafts and a freely diffusible Epac2-based probe to monitor total cytosolic cAMP. β1AR and EPR activation elicited responses detected by both FRET probes. However, cholesterol depletion only affected β1AR responses detected by the PKA probe. These results indicate that lipid rafts alone are not sufficient to explain the difference between β1AR and EPR responses. They also suggest that β1AR regulation of myocyte contraction involves the local production of cAMP by a subpopulation of receptors associated with caveolar lipid rafts. PMID:21115018

  20. Study of compartmentalization in the visna clinical form of small ruminant lentivirus infection in sheep

    PubMed Central

    2012-01-01

    Background A central nervous system (CNS) disease outbreak caused by small ruminant lentiviruses (SRLV) has triggered interest in Spain due to the rapid onset of clinical signs and relevant production losses. In a previous study on this outbreak, the role of LTR in tropism was unclear and env encoded sequences, likely involved in tropism, were not investigated. This study aimed to analyze heterogeneity of SRLV Env regions - TM amino terminal and SU V4, C4 and V5 segments - in order to assess virus compartmentalization in CNS. Results Eight Visna (neurologically) affected sheep of the outbreak were used. Of the 350 clones obtained after PCR amplification, 142 corresponded to CNS samples (spinal cord and choroid plexus) and the remaining to mammary gland, blood cells, bronchoalveolar lavage cells and/or lung. The diversity of the env sequences from CNS was 11.1-16.1% between animals and 0.35-11.6% within each animal, except in one animal presenting two sequence types (30% diversity) in the CNS (one grouping with those of the outbreak), indicative of CNS virus sequence heterogeneity. Outbreak sequences were of genotype A, clustering per animal and compartmentalizing in the animal tissues. No CNS specific signature patterns were found. Conclusions Bayesian approach inferences suggested that proviruses from broncoalveolar lavage cells and peripheral blood mononuclear cells represented the common ancestors (infecting viruses) in the animal and that neuroinvasion in the outbreak involved microevolution after initial infection with an A-type strain. This study demonstrates virus compartmentalization in the CNS and other body tissues in sheep presenting the neurological form of SRLV infection. PMID:22281181

  1. Excimer laser channel creation in polyethersulfone hollow fibers for compartmentalized in vitro neuronal cell culture scaffolds.

    PubMed

    Brayfield, Candace A; Marra, Kacey G; Leonard, John P; Tracy Cui, X; Gerlach, Jörg C

    2008-03-01

    Hollow fiber scaffolds that compartmentalize axonal processes from their cell bodies can enable neuronal cultures with directed neurite outgrowth within a three-dimensional (3-D) space for controlling neuronal cell networking in vitro. Controllable 3-D neuronal networks in vitro could provide tools for studying neurobiological events. In order to create such a scaffold, polyethersulfone (PES) microporous hollow fibers were ablated with a KrF excimer laser to generate specifically designed channels for directing neurite outgrowth into the luminal compartments of the fibers. Excimer laser modification is demonstrated as a reproducible method to generate 5microm diameter channels within PES hollow fiber walls that allow compartmentalization of neuronal cell bodies from their axons. Laser modification of counterpart flat sheet PES membranes with peak surface fluences of 1.2Jcm(-2) results in increased hydrophobicity and laminin adsorption on the surface compared with the unmodified PES surface. This is correlated to enhanced PC12 cell adhesion with increasing fluence onto laser-modified PES membrane surfaces coated with laminin when compared with unmodified surfaces. Adult rat neural progenitor cells differentiated on PES fibers with laser-created channels resulted in spontaneous cell process growth into the channels of the scaffold wall while preventing entrance of cell bodies. Therefore, laser-modified PES fibers serve as scaffolds with channels conducive to directing neuronal cell process growth. These hollow fiber scaffolds can potentially be used in combination with perfusion and oxygenation hollow fiber membrane sets to construct a hollow fiber-based 3-D bioreactor for controlling and studying in vitro neuronal networking in three dimensions between compartmentalized cultures. PMID:18060849

  2. Regulation of NAD+ metabolism, signaling and compartmentalization in the yeast Saccharomyces cerevisiae

    PubMed Central

    Kato, Michiko; Lin, Su-Ju

    2014-01-01

    Pyridine nucleotides are essential coenzymes in many cellular redox reactions in all living systems. In addition to functioning as a redox carrier, NAD+ is also a required co-substrate for the conserved sirtuin deacetylases. Sirtuins regulate transcription, genome maintenance and metabolism and function as molecular links between cells and their environment. Maintaining NAD+ homeostasis is essential for proper cellular function and aberrant NAD+ metabolism has been implicated in a number of metabolic- and age-associated diseases. Recently, NAD+ metabolism has been linked to the phosphate-responsive signaling pathway (PHO pathway) in the budding yeast Saccharomyces cerevisiae. Activation of the PHO pathway is associated with the production and mobilization of the NAD+ metabolite nicotinamide riboside (NR), which is mediated in part by PHO-regulated nucleotidases. Cross-regulation between NAD+ metabolism and the PHO pathway has also been reported; however, detailed mechanisms remain to be elucidated. The PHO pathway also appears to modulate the activities of common downstream effectors of multiple nutrient-sensing pathways (Ras-PKA, TOR, Sch9/AKT). These signaling pathways were suggested to play a role in calorie restriction-mediated beneficial effects, which have also been linked to Sir2 function and NAD+ metabolism. Here, we discuss the interactions of these pathways and their potential roles in regulating NAD+ metabolism. In eukaryotic cells, intracellular compartmentalization facilitates the regulation of enzymatic functions and also concentrates or sequesters specific metabolites. Various NAD+-mediated cellular functions such as mitochondrial oxidative phosphorylation are compartmentalized. Therefore, we also discuss several key players functioning in mitochondrial, cytosolic and vacuolar compartmentalization of NAD+ intermediates, and their potential roles in NAD+ homeostasis. To date, it remains unclear how NAD+ and NAD+ intermediates shuttle between different

  3. Directed clustering in driven compartmentalized granular gas systems in zero gravity

    NASA Astrophysics Data System (ADS)

    Li, Y.; Hou, M.; Evesque, P.

    2011-12-01

    Clustering of shaken fluidized granular matter in connected compartments has been observed and studied in the laboratory. This clustering behavior in granular gas systems is related to the dissipative nature of granular system, and therefore shall not depend on gravity. This clustering phenomenon in compartmental configuration may provide a means for particle depletion and transportation in microgravity environment. In this work we propose different configurations for possible directed clustering in zero gravity. The related experiment has been planned for the Chinese satellite SJ-10.

  4. Stop and restart of granular clock in a vibrated compartmentalized bidisperse granular system

    NASA Astrophysics Data System (ADS)

    Liu, Qi-Yi; Hu, Mao-Bin; Jiang, Rui; Wu, Yong-Hong

    2013-01-01

    This paper studies a bidisperse granular mixture consisting of two species of stainless steel spheres in a vertically vibrated compartmentalized container. The experiments show that with proper vibration acceleration, the granular clock stops when horizontal segregation of the large spheres residing in the far end from the barrier wall occurs. When the segregation is broken, the granular clock restarts. We present the phase diagrams of vibration acceleration versus container width and small particle number, which exhibits three different regions, namely, clustering state, stop-restart of the granular clock, and the granular clock. A generalized flux model is proposed to reproduce the phenomenon of stop and restart of the granular clock.

  5. In or out? On the tightness of glycosomal compartmentalization of metabolites and enzymes in Trypanosoma brucei.

    PubMed

    Haanstra, Jurgen R; Bakker, Barbara M; Michels, Paul A M

    2014-11-01

    Trypanosomatids sequester large parts of glucose metabolism inside specialised peroxisomes, called glycosomes. Many studies have shown that correct glycosomal compartmentalization of glycolytic enzymes is essential for bloodstream-form Trypanosoma brucei. The recent finding of pore-forming activities in glycosomal membrane preparations and extensions of the trypanosome glycolysis computer model with size-selective pores sparked again an old debate on the extent of (im)permeability of the glycosomal membrane and whether glycosomally located glycolytic enzymes could and should also be present with some activity in the cytosol. This review presents a critical discussion of the experimental and theoretical evidence for and against the different hypotheses. PMID:25476771

  6. Compartmentalized Cerebral Metabolism of [1,6-13C]Glucose Determined by in vivo 13C NMR Spectroscopy at 14.1 T

    PubMed Central

    Duarte, João M. N.; Lanz, Bernard; Gruetter, Rolf

    2011-01-01

    Cerebral metabolism is compartmentalized between neurons and glia. Although glial glycolysis is thought to largely sustain the energetic requirements of neurotransmission while oxidative metabolism takes place mainly in neurons, this hypothesis is matter of debate. The compartmentalization of cerebral metabolic fluxes can be determined by 13C nuclear magnetic resonance (NMR) spectroscopy upon infusion of 13C-enriched compounds, especially glucose. Rats under light α-chloralose anesthesia were infused with [1,6-13C]glucose and 13C enrichment in the brain metabolites was measured by 13C NMR spectroscopy with high sensitivity and spectral resolution at 14.1 T. This allowed determining 13C enrichment curves of amino acid carbons with high reproducibility and to reliably estimate cerebral metabolic fluxes (mean error of 8%). We further found that TCA cycle intermediates are not required for flux determination in mathematical models of brain metabolism. Neuronal tricarboxylic acid cycle rate (VTCA) and neurotransmission rate (VNT) were 0.45 ± 0.01 and 0.11 ± 0.01 μmol/g/min, respectively. Glial VTCA was found to be 38 ± 3% of total cerebral oxidative metabolism, accounting for more than half of neuronal oxidative metabolism. Furthermore, glial anaplerotic pyruvate carboxylation rate (VPC) was 0.069 ± 0.004 μmol/g/min, i.e., 25 ± 1% of the glial TCA cycle rate. These results support a role of glial cells as active partners of neurons during synaptic transmission beyond glycolytic metabolism. PMID:21713114

  7. Recovery of fish communities in the Finniss River, northern Australia, following remediation of the Rum Jungle uranium/copper mine site.

    PubMed

    Jeffree, R A; Twining, J R; Thomson, J

    2001-07-15

    The Finniss River in the wet-dry tropics of northern Australia has received acid rock drainage (ARD) contaminants from the Rum Jungle uranium/copper mine site over more than four decades. Annual-cycle loads of Cu, Zn, Mn, and sulfate, calculated from daily water and flow measurements, have been determined both prior to and following mine-site remediation, that began in the early 1980s. The effects of varying contaminant loads on the relative abundances of seven fish species, sampled by enmeshing nets during dry seasons, were determined by nonmetric multidimensional scaling (nMDS), in combination with cluster-analysis and other nonparametric statistical techniques. These analyses showed that (i) prior to remediation, the impacted region of the Finniss River in 1974 had significantly dissimilar (P < 0.001) and more heterogeneous fish communities, generally characterized by reduced diversity and abundance, compared to sites unexposed to elevated contaminant water concentrations and (ii) postremediation, recovery in fish communities from the impacted region was indicated because they were not significantly dissimilar from those sampled at contemporary (P = 0.16) unimpacted sites, that were also similar to preremedial unimpacted sites. Even though considerable contaminant loads are still being delivered to the impacted region of the Finniss River over the annual cycle, the recovery in fish diversity and abundances is consistent with (a) reductions of in situ contaminant water concentrations at the time of fish sampling, (b) reductions in annual-cycle contaminant loads of sulfate, Cu, Zn, and Mn by factors of 3-7, (c) greatly reduced frequencies of occurrence and magnitude of elevated contaminant water concentrations over the annual cycle, that was most pronounced for Cu, and (d) the absence of extensive fish-kills during the first-flushes of contaminants into the Finniss river proper at the beginning of the wet season, that were observed prior to remediation. As such

  8. A lipid based multi-compartmental system: Liposomes-in-double emulsion for oral vaccine delivery.

    PubMed

    Liau, Jin Jau; Hook, Sarah; Prestidge, Clive A; Barnes, Timothy J

    2015-11-01

    The gastric mucosa provides the entry point for the majority of pathogens, as well as being the induction site for protective immunity; however, there remain few examples of oral vaccines due to the challenges presented by the gastrointestinal route. In this study, we develop a lipid-based multi-compartmental system for oral vaccine delivery. Specifically, we have optimised the formulation of a water-in-oil-in-water double emulsion prepared from a triglyceride - soya bean oil, using surfactants Span 80/Tween 80 and Pluronic F127 to stabilise the internal and external water phases, respectively. Into the internal water phase, we also incorporated a PEGylated liposome, prepared using hydrogenated phosphatidyl choline as a carrier for our model protein, FITC-labelled ovalbumin. We demonstrated the successful incorporation of intact liposomes into the internal water phase of the double emulsion using imaging techniques including cryo-SEM and confocal microscopy. Finally, we use in vitro release studies of FITC-ovalbumin, to provide further confirmation of the multi-compartmental structure of the double emulsion system and demonstrate significant extended release of the entrapped model antigen compared with PEG-liposomes; these characteristics are attractive for oral vaccine delivery. PMID:26455337

  9. Compartmentalization and molecular traffic in secondary metabolism: a new understanding of established cellular processes

    PubMed Central

    Roze, Ludmila V.; Chanda, Anindya; Linz, John E.

    2010-01-01

    Great progress has been made in understanding the regulation of expression of genes involved in secondary metabolism. Less is known about the mechanisms that govern the spatial distribution of the enzymes, cofactors, and substrates that mediate catalysis of secondary metabolites within the cell. Filamentous fungi in the genus Aspergillus synthesize an array of secondary metabolites and provide useful systems to analyze the mechanisms that mediate the temporal and spatial regulation of secondary metabolism in eukaryotes. For example, aflatoxin biosynthesis in A. parasiticus has been studied intensively because this mycotoxin is highly toxic, mutagenic, and carcinogenic in humans and animals. Using aflatoxin synthesis to illustrate key concepts, this review focuses on the mechanisms by which sub-cellular compartmentalization and intra-cellular molecular traffic contribute to the initiation and completion of secondary metabolism within the cell. We discuss the recent discovery of aflatoxisomes, specialized trafficking vesicles that participate in the compartmentalization of aflatoxin synthesis and export of the toxin to the cell exterior; this work provides a new and clearer understanding of how cells integrate secondary metabolism into basic cellular metabolism via the intracellular trafficking machinery. PMID:20519149

  10. Compartmentalized self-replication: a novel method for the directed evolution of polymerases and other enzymes.

    PubMed

    Ghadessy, Farid J; Holliger, Philipp

    2007-01-01

    Compartmentalized self-replication (CSR) is a novel method for the directed evolution of enzymes and, in particular, polymerases. In its simplest form, CSR consists of a simple feedback loop involving a polymerase that replicates only its own encoding gene (self-replication). Self-replication occurs in discrete, spatially separate, noncommunicating compartments formed by a heat-stable water-in-oil emulsion. Compartmentalization ensures the linkage of phenotype and genotype (i.e., it ensures that each polymerase replicates only its own encoding gene to the exclusion of those in the other compartments). As a result, adaptive gains by the polymerase directly (and proportionally) translate into genetic amplification of the encoding polymerase gene. CSR has proven to be a useful strategy for the directed evolution of polymerases directly from diverse repertoires of polymerase genes. In this chapter, we describe some of the CSR protocols used successfully to evolve variants of T. aquaticus Pol I (Taq) polymerase with novel and useful properties, such as increased thermostability or resistance to the potent inhibitor, heparin, from a repertoire of randomly mutated Taq polymerase genes. PMID:17041269

  11. Metabolism of monoterpenes: evidence for compartmentation of l-menthone metabolism in peppermint (Mentha piperita) leaves

    SciTech Connect

    Martinkus, C.; Croteau, R.

    1981-01-01

    Previous studies have shown that the monoterpene ketone l-(G-/sup 3/H)-menthone is reduced to the epimeric alcohols l-menthol and d-neomenthol in leaf discs of flowering peppermint (Mentha piperita L.), and that a portion of the menthol is converted to menthyl acetate while the bulk of the neomenthol is transformed to neomenthyl-..beta..-D-glucoside. When l-(3-/sup 3/H)menthol and d-(3-/sup 3/H)neomenthol are separately administered to leaf discs, both menthyl and neomenthyl acetates and menthyl and neomenthyl glucosides are formed with nearly equal facility, suggesting that the metabolic specificity observed with the ketone precursor was not a function of the specificity of the transglucosylase or transacetylase but rather a result of compartmentation of each stereospecific dehydrogenase with the appropriate transferase. Co-purification of the acceptor-mediated activities, and differential activation and inhibition studies, provided strong evidence that the same UDP-glucose-dependent enzyme could transfer glucose to either l-menthol or d-neometnthol. These results demonstrate that the specific in vivo conversion of l-menthone to l-menthyl acetate and d-neomenthyl-..beta..-D-glucoside cannot be attributed to the selectivity of the transferases, and they clearly indicate that the metabolic specificity observed is a result of compartmentation effects.

  12. A compartmental-spatial system dynamics approach to ground water modeling.

    PubMed

    Roach, Jesse; Tidwell, Vince

    2009-01-01

    High-resolution, spatially distributed ground water flow models can prove unsuitable for the rapid, interactive analysis that is increasingly demanded to support a participatory decision environment. To address this shortcoming, we extend the idea of multiple cell (Bear 1979) and compartmental (Campana and Simpson 1984) ground water models developed within the context of spatial system dynamics (Ahmad and Simonovic 2004) for rapid scenario analysis. We term this approach compartmental-spatial system dynamics (CSSD). The goal is to balance spatial aggregation necessary to achieve a real-time integrative and interactive decision environment while maintaining sufficient model complexity to yield a meaningful representation of the regional ground water system. As a test case, a 51-compartment CSSD model was built and calibrated from a 100,0001 cell MODFLOW (McDonald and Harbaugh 1988) model of the Albuquerque Basin in central New Mexico (McAda and Barroll 2002). Seventy-seven percent of historical drawdowns predicted by the MODFLOW model were within 1 m of the corresponding CSSD estimates, and in 80% of the historical model run years the CSSD model estimates of river leakage, reservoir leakage, ground water flow to agricultural drains, and riparian evapotranspiration were within 30% of the corresponding estimates from McAda and Barroll (2002), with improved model agreement during the scenario period. Comparisons of model results demonstrate both advantages and limitations of the CCSD model approach. PMID:19459984

  13. Synaptic compartmentalization by micropatterned masking of a surface adhesive cue in cultured neurons.

    PubMed

    Ryu, Jae Ryun; Jang, Min Jee; Jo, Youhwa; Joo, Sunghoon; Lee, Do Hoon; Lee, Byung Yang; Nam, Yoonkey; Sun, Woong

    2016-06-01

    Functions of neuronal circuit are fundamentally modulated by its quality and quantity of connections. Assessment of synapse, the basic unit for a neuronal connection, is labor-intensive and time-consuming in conventional culture systems, due to the small size and the spatially random distribution. In the present study, we propose a novel 'synapse compartmentalization' culture system, in which synapses are concentrated at controlled locations. We fabricated a negative dot array pattern by coating the entire surface with poly-l-lysine (PLL) and subsequent microcontact printing of 1) substrates which mask positive charge of PLL (Fc, BSA and laminin), or 2) a chemorepulsive protein (Semaphorin 3F-Fc). By combination of physical and biological features of these repulsive substrates, functional synapses were robustly concentrated in the PLL-coated dots. This synapse compartmentalization chip can be combined with the various high-throughput assay formats based on the synaptic morphology and function. Therefore, this quantifiable and controllable dot array pattern by microcontact printing will be potential useful for bio-chip platforms for the high-density assays used in synapse-related neurobiological studies. PMID:27035488

  14. Modulation in Wistar Rats of Blood Corticosterone Compartmentation by Sex and a Cafeteria Diet

    PubMed Central

    Romero, María del Mar; Holmgren-Holm, Fredrik; Grasa, Maria del Mar; Esteve, Montserrat; Remesar, Xavier; Fernández-López, José Antonio; Alemany, Marià

    2013-01-01

    In the metabolic syndrome, glucocorticoid activity is increased, but circulating levels show little change. Most of blood glucocorticoids are bound to corticosteroid-binding globulin (CBG), which liver expression and circulating levels are higher in females than in males. Since blood hormones are also bound to blood cells, and the size of this compartment is considerable for androgens and estrogens, we analyzed whether sex or eating a cafeteria diet altered the compartmentation of corticosterone in rat blood. The main corticosterone compartment in rat blood is that specifically bound to plasma proteins, with smaller compartments bound to blood cells or free. Cafeteria diet increased the expression of liver CBG gene, binding plasma capacity and the proportion of blood cell-bound corticosterone. There were marked sex differences in blood corticosterone compartmentation in rats, which were unrelated to testosterone. The use of a monoclonal antibody ELISA and a polyclonal Western blot for plasma CBG compared with both specific plasma binding of corticosterone and CBG gene expression suggested the existence of different forms of CBG, with varying affinities for corticosterone in males and females, since ELISA data showed higher plasma CBG for males, but binding and Western blot analyses (plus liver gene expression) and higher physiological effectiveness for females. Good cross- reactivity to the antigen for polyclonal CBG antibody suggests that in all cases we were measuring CBG.The different immunoreactivity and binding affinity may help explain the marked sex-related differences in plasma hormone binding as sex-linked different proportions of CBG forms. PMID:23451210

  15. Intramuscular Innervation of Primate Extraocular Muscles: Unique Compartmentalization in Horizontal Recti

    PubMed Central

    da Silva Costa, Roberta Martins; Kung, Jennifer; Poukens, Vadims; Yoo, Lawrence; Tychsen, Lawrence

    2011-01-01

    Purpose. It has been proposed that the lateral rectus (LR), like many skeletal and craniofacial muscles, comprises multiple neuromuscular compartments subserving different physiological functions. To explore the anatomic potential of compartmentalization in all four rectus extraocular muscles (EOMs), evidence was sought of possible regional selectivity in intramuscular innervation of all rectus EOMs. Methods. Whole orbits of two humans and one macaque monkey were serially sectioned at 10 μm thickness and stained with Masson's trichrome. Three-dimensional reconstruction was performed of the intramuscular courses of motor nerves from the deep orbit to the anterior extents of their arborizations within all four rectus EOMs in each orbit. Results. Findings concorded in monkey and human orbits. Externally to the global surface of the lateral (LR) and medial rectus (MR) EOMs, motor nerve trunks bifurcated into approximately equal-sized branches before entering the global layer and observing a segregation of subsequent arborization into superior zones that exhibited minimal overlap along the length of the LR and only modest overlap for MR. In contrast, intramuscular branches of the superior and the nasal portion of the inferior rectus were highly mixed. Conclusions. Consistent segregation of intramuscular motor nerve arborization suggests functionally distinct superior and inferior zones within the horizontal rectus EOMs in both humans and monkeys. Reduced or absent compartmentalization in vertical rectus EOMs supports a potential functional role for differential innervation in horizontal rectus zones that could mediate previously unrecognized vertical oculorotary actions. PMID:21220556

  16. Subcellular compartmentalization in protoplasts from Artemisia annua cell cultures: engineering attempts using a modified SNARE protein.

    PubMed

    Di Sansebastiano, Gian Pietro; Rizzello, Francesca; Durante, Miriana; Caretto, Sofia; Nisi, Rossella; De Paolis, Angelo; Faraco, Marianna; Montefusco, Anna; Piro, Gabriella; Mita, Giovanni

    2015-05-20

    Plants are ideal bioreactors for the production of macromolecules but transport mechanisms are not fully understood and cannot be easily manipulated. Several attempts to overproduce recombinant proteins or secondary metabolites failed. Because of an independent regulation of the storage compartment, the product may be rapidly degraded or cause self-intoxication. The case of the anti-malarial compound artemisinin produced by Artemisia annua plants is emblematic. The accumulation of artemisinin naturally occurs in the apoplast of glandular trichomes probably involving autophagy and unconventional secretion thus its production by undifferentiated tissues such as cell suspension cultures can be challenging. Here we characterize the subcellular compartmentalization of several known fluorescent markers in protoplasts derived from Artemisia suspension cultures and explore the possibility to modify compartmentalization using a modified SNARE protein as molecular tool to be used in future biotechnological applications. We focused on the observation of the vacuolar organization in vivo and the truncated form of AtSYP51, 51H3, was used to induce a compartment generated by the contribution of membrane from endocytosis and from endoplasmic reticulum to vacuole trafficking. The artificial compartment crossing exocytosis and endocytosis may trap artemisinin stabilizing it until extraction; indeed, it is able to increase total enzymatic activity of a vacuolar marker (RGUSChi), probably increasing its stability. Exploring the 51H3-induced compartment we gained new insights on the function of the SNARE SYP51, recently shown to be an interfering-SNARE, and new hints to engineer eukaryote endomembranes for future biotechnological applications. PMID:25451863

  17. A compartmental model for oxygen-carbon dioxide coupled transport in the microcirculation.

    PubMed

    Ye, G F; Moore, T W; Buerk, D G; Jaron, D

    1994-01-01

    We present a multicompartmental model for an oxygen-carbon dioxide transport system. The compartmental equations and their lumped parameters are derived through space averaging of the corresponding distributed model. The model can predict compartmental distributions of oxygen and carbon dioxide partial pressures, oxygen-hemoglobin saturation, and pH. Other unique features include the effects of the radial distribution of partial pressures and the difference in metabolic rates between vessel wall and tissue. A model for the cat brain, based on this formulation, is compared with results of experiments and with two types of earlier models: one without space averaging and one without carbon dioxide transport. The results suggest that space averaging the convective terms significantly affects the behavior of the model. This is consistent with conclusions from our earlier oxygen-only model. Our observations also demonstrate, however, significant differences between the results from the oxygen-carbon dioxide model and the oxygen-only model. For instance, at low blood flow rates or at low level of oxygen input, predicted oxygen partial pressures can differ by as much as 30% between the two models. Results obtained from the present model are supported by available experimental findings. PMID:7825749

  18. Intracellular Redox Compartmentation and ROS-Related Communication in Regulation and Signaling1[OPEN

    PubMed Central

    2016-01-01

    Recent years have witnessed enormous progress in understanding redox signaling related to reactive oxygen species (ROS) in plants. The consensus view is that such signaling is intrinsic to many developmental processes and responses to the environment. ROS-related redox signaling is tightly wedded to compartmentation. Because membranes function as barriers, highly redox-active powerhouses such as chloroplasts, peroxisomes, and mitochondria may elicit specific signaling responses. However, transporter functions allow membranes also to act as bridges between compartments, and so regulated capacity to transmit redox changes across membranes influences the outcome of triggers produced at different locations. As well as ROS and other oxidizing species, antioxidants are key players that determine the extent of ROS accumulation at different sites and that may themselves act as signal transmitters. Like ROS, antioxidants can be transported across membranes. In addition, the intracellular distribution of antioxidative enzymes may be modulated to regulate or facilitate redox signaling appropriate to the conditions. Finally, there is substantial plasticity in organellar shape, with extensions such as stromules, peroxules, and matrixules playing potentially crucial roles in organelle-organelle communication. We provide an overview of the advances in subcellular compartmentation, identifying the gaps in our knowledge and discussing future developments in the area. PMID:27208308

  19. Vacuolar compartmentalization as indispensable component of heavy metal detoxification in plants.

    PubMed

    Sharma, Shanti S; Dietz, Karl-Josef; Mimura, Tetsuro

    2016-05-01

    Plant cells orchestrate an array of molecular mechanisms for maintaining plasmatic concentrations of essential heavy metal (HM) ions, for example, iron, zinc and copper, within the optimal functional range. In parallel, concentrations of non-essential HMs and metalloids, for example, cadmium, mercury and arsenic, should be kept below their toxicity threshold levels. Vacuolar compartmentalization is central to HM homeostasis. It depends on two vacuolar pumps (V-ATPase and V-PPase) and a set of tonoplast transporters, which are directly driven by proton motive force, and primary ATP-dependent pumps. While HM non-hyperaccumulator plants largely sequester toxic HMs in root vacuoles, HM hyperaccumulators usually sequester them in leaf cell vacuoles following efficient long-distance translocation. The distinct strategies evolved as a consequence of organ-specific differences particularly in vacuolar transporters and in addition to distinct features in long-distance transport. Recent molecular and functional characterization of tonoplast HM transporters has advanced our understanding of their contribution to HM homeostasis, tolerance and hyperaccumulation. Another important part of the dynamic vacuolar sequestration syndrome involves enhanced vacuolation. It involves vesicular trafficking in HM detoxification. The present review provides an updated account of molecular aspects that contribute to the vacuolar compartmentalization of HMs. PMID:26729300

  20. Detecting compartmental non-Gaussian diffusion with symmetrized double-PFG MRI.

    PubMed

    Paulsen, Jeffrey L; Özarslan, Evren; Komlosh, Michal E; Basser, Peter J; Song, Yi-Qiao

    2015-11-01

    Diffusion in tissue and porous media is known to be non-Gaussian and has been used for clinical indications of stroke and other tissue pathologies. However, when conventional NMR techniques are applied to biological tissues and other heterogeneous materials, the presence of multiple compartments (pores) with different Gaussian diffusivities will also contribute to the measurement of non-Gaussian behavior. Here we present symmetrized double PFG (sd-PFG), which can separate these two contributions to non-Gaussian signal decay as having distinct angular modulation frequencies. In contrast to prior angular d-PFG methods, sd-PFG can unambiguously extract kurtosis as an oscillation from samples with isotropic or uniformly oriented anisotropic pores, and can generally extract a combination of compartmental anisotropy and kurtosis. The method further fixes its sensitivity with respect to the time dependence of the apparent diffusion coefficient. We experimentally demonstrate the measurement of the fourth cumulant (kurtosis) of diffusion and find it consistent with theoretical predictions. By enabling the unambiguous identification of contributions of compartmental kurtosis to the signal, sd-PFG has the potential to help identify the underlying micro-structural changes corresponding to current kurtosis based diagnostics, and act as a novel source of contrast to better resolve tissue micro-structure. PMID:26434812

  1. HIV-1 in genital tract and plasma of women: Compartmentalization of viral sequences, coreceptor usage, and glycosylation

    PubMed Central

    Kemal, Kimdar Sherefa; Foley, Brian; Burger, Harold; Anastos, Kathryn; Minkoff, Howard; Kitchen, Christina; Philpott, Sean M.; Gao, Wei; Robison, Esther; Holman, Susan; Dehner, Carolyn; Beck, Suzanne; Meyer, William A.; Landay, Alan; Kovacs, Andrea; Bremer, James; Weiser, Barbara

    2003-01-01

    Worldwide, 90% of HIV-1 infections are transmitted heterosexually. Because the genital mucosa are the sites of initial contact with HIV-1 for most exposed individuals, study of the virus from the genital tract is critical for the development of vaccines and therapeutics. Previous analyses of HIV-1 in various tissues have documented compartmentalization of viral genomes. Whether compartmentalization was associated with viral phenotypic differences or immune status, however, was not well understood. We compared HIV-1 gp120 env sequences from the genital tract and plasma of 12 women. Eight women displayed compartmentalized HIV-1 RNA genomes, with viral sequences from each site that were clearly discrete, yet phylogenetically related. The remaining four exhibited env sequences that were intermingled between the two sites. Women with compartmentalized HIV-1 genomes had higher CD4+ cell counts than those displaying intermingled strains (P = 0.02). Intrapatient HIV-1 recombinants comprising sequences that were characteristic of both sites were identified. We next compared viral phenotypes in each compartment. HIV-1 coreceptor usage was often compartmentalized (P ≤ 0.01). The number of N-linked glycosylation sites, associated with neutralization resistance, also differed between compartments (P < 0.01). Furthermore, disparities between the density of gp120 glycosylations in each compartment correlated with higher CD4+ counts (P = 0.03). These data demonstrate that the genital tract and plasma can harbor populations of replicating HIV-1 with different phenotypes. The association of higher CD4+ cell counts with compartmentalization of viral genomes and density of gp120 glycosylations suggests that the immune response influences the development of viral genotypes in each compartment. These findings are relevant to the prevention and control of HIV-1 infection. PMID:14557540

  2. Effect of Culture Conditions on the Production of an Extracellular Protease by Bacillus sp. Isolated from Soil Sample of Lavizan Jungle Park

    PubMed Central

    Akhavan Sepahy, Abbas; Jabalameli, Leila

    2011-01-01

    Soil samples of Tehran jungle parks were screened for proteolytic Bacilli. Among eighteen protease producers one of the isolates obtained from Lavizan park, in north east of Tehran, was selected for further experimental studies. This isolate was identified as Bacillus sp. strain CR-179 based on partial sequencing of 16S rRNA. Various nutritional and environmental parameters affected protease production by Bacillus sp. strain CR-179. Protease production by this Bacillus cultivated in liquid cultures reached a maximum at 24 h, with levels of 340.908 U/mL. Starch and maltose were the best substrates for enzyme production while some pure sugars such as fructose, glucose, and sucrose could not influence production of protease. Among various organic nitrogen sources corn steep liquor, which is commercial, was found as the best substrate followed by yeast extract, whey protein, and beef extract. The optimal pH and optimal temperature of enzyme production were 8.0 and 45°C, respectively. Studies on enzymatic characterization revealed that crude protease showed maximum activity at pH 9.0 and 60°C, which is indicating the enzyme to be thermoalkaline protease. PMID:22191016

  3. The Role of Nuclear Bodies in Gene Expression and Disease

    PubMed Central

    Morimoto, Marie; Boerkoel, Cornelius F.

    2013-01-01

    This review summarizes the current understanding of the role of nuclear bodies in regulating gene expression. The compartmentalization of cellular processes, such as ribosome biogenesis, RNA processing, cellular response to stress, transcription, modification and assembly of spliceosomal snRNPs, histone gene synthesis and nuclear RNA retention, has significant implications for gene regulation. These functional nuclear domains include the nucleolus, nuclear speckle, nuclear stress body, transcription factory, Cajal body, Gemini of Cajal body, histone locus body and paraspeckle. We herein review the roles of nuclear bodies in regulating gene expression and their relation to human health and disease. PMID:24040563

  4. Compartmentalized PDE4A5 Signaling Impairs Hippocampal Synaptic Plasticity and Long-Term Memory

    PubMed Central

    Park, Alan J.; Tolentino, Rosa E.; Bruinenberg, Vibeke M.; Tudor, Jennifer C.; Lee, Yool; Hansen, Rolf T.; Guercio, Leonardo A.; Linton, Edward; Neves-Zaph, Susana R.; Meerlo, Peter; Baillie, George S.; Houslay, Miles D.

    2016-01-01

    Alterations in cAMP signaling are thought to contribute to neurocognitive and neuropsychiatric disorders. Members of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains >25 different isoforms, play a key role in determining spatial cAMP degradation so as to orchestrate compartmentalized cAMP signaling in cells. Each isoform binds to a different set of protein complexes through its unique N-terminal domain, thereby leading to targeted degradation of cAMP in specific intracellular compartments. However, the functional role of specific compartmentalized PDE4 isoforms has not been examined in vivo. Here, we show that increasing protein levels of the PDE4A5 isoform in mouse hippocampal excitatory neurons impairs a long-lasting form of hippocampal synaptic plasticity and attenuates hippocampus-dependent long-term memories without affecting anxiety. In contrast, viral expression of a truncated version of PDE4A5, which lacks the unique N-terminal targeting domain, does not affect long-term memory. Further, overexpression of the PDE4A1 isoform, which targets a different subset of signalosomes, leaves memory undisturbed. Fluorescence resonance energy transfer sensor-based cAMP measurements reveal that the full-length PDE4A5, in contrast to the truncated form, hampers forskolin-mediated increases in neuronal cAMP levels. Our study indicates that the unique N-terminal localization domain of PDE4A5 is essential for the targeting of specific cAMP-dependent signaling underlying synaptic plasticity and memory. The development of compounds to disrupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domains may provide a fruitful approach to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling. SIGNIFICANCE STATEMENT Neurons exhibit localized signaling processes that enable biochemical cascades to be activated selectively in specific subcellular

  5. Lattice theory of reaction efficiency in compartmentalized systems. II. Reduction of dimensionality

    NASA Astrophysics Data System (ADS)

    Lee, Pil H.; Kozak, John J.

    1984-01-01

    The timing and efficiency of a diffusion-controlled kinetic process in a compartmentalized system can be enhanced by reducing the dimensionality of the reaction space of the system. This idea, introduced by Adam and Delbrück and referred to as ``reduction of dimensionality,'' is explored quantitatively in this paper using a lattice theory of reaction efficiency developed in our earlier work. In particular, we study the interplay between system geometry and reaction efficiency using an approach in which group theoretic arguments are used within the framework of the theory of finite Markov processes to determine the average number of steps required for a diffusing coreactant A to undergo an irreversible reaction with a stationary target molecule B. We study in detail three classes of problems in this paper. First, we study as a function of the position of the reaction center how the efficiency of the underlying, irreversible, reaction-diffusion process A+B → C changes with increase in system size for symmetrical geometries. We show how reducing the dimensionality of the flow of the diffusing co-reactant leads to a crossover in reaction efficiency with increase in the size of the system, and document this effect as a function of N (the total number of sites characterizing the reaction space of the system), d (the dimensionality of the system), and ν (the valency or connectivity between adjacent sites in the reaction space). Secondly, we study how the calculated value of , and hence the efficiency of the process, changes when the compartmentalized system is characterized by tubular or platelet geometries, and show how the process of reduction of dimensionality is dependent on the further geometrical characteristics of eccentricity ɛ and the surface-to-volume ratio S/V. Finally, we study the consequences of reduction of dimensionality for (two) consecutive (say, enzymatic) reactions taking place in a compartmentalized system and demonstrate the advantages of

  6. Sequence Stratigraphy of the Dakota Sandstone, Eastern San Juan Basin, New Mexico, and its Relationship to Reservoir Compartmentalization

    SciTech Connect

    Varney, Peter J.

    2002-04-23

    This research established the Dakota-outcrop sequence stratigraphy in part of the eastern San Juan Basin, New Mexico, and relates reservoir quality lithologies in depositional sequences to structure and reservoir compartmentalization in the South Lindrith Field area. The result was a predictive tool that will help guide further exploration and development.

  7. Lipid droplet-associated proteins (LDAPs) are required for the dynamic regulation of neutral lipid compartmentation in plant cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Eukaryotic cells compartmentalize neutral lipids into organelles called lipid droplets (LDs), and while much is known about the role of LDs in storing triacylglycerols (TAGs) in seeds, their biogenesis and function in non-seed tissues is poorly understood. Recently, we identified a class of plant-sp...

  8. Ultrasensitive quantification of TAP-dependent antigen compartmentalization in scarce primary immune cell subsets.

    PubMed

    Fischbach, Hanna; Döring, Marius; Nikles, Daphne; Lehnert, Elisa; Baldauf, Christoph; Kalinke, Ulrich; Tampé, Robert

    2015-01-01

    Presentation of peptides on major histocompatibility complex class I (MHC I) is essential for the establishment and maintenance of self-tolerance, priming of antigen-specific CD8(+) T cells and the exertion of several T-cell effector functions. Cytosolic proteasomes continuously degrade proteins into peptides, which are actively transported across the endoplasmic reticulum (ER) membrane by the transporter associated with antigen processing (TAP). In the ER lumen antigenic peptides are loaded onto MHC I, which is displayed on the cell surface. Here we describe an innovative flow cytometric approach to monitor time-resolved ER compartmentalization of antigenic peptides. This assay allows the analysis of distinct primary human immune cell subsets at reporter peptide concentrations of 1 nM. Thus, this ultrasensitive method for the first time permits quantification of TAP activity under close to physiological conditions in scarce primary cell subsets such as antigen cross-presenting dendritic cells. PMID:25656091

  9. Compartmentalized liquid crystal alignment induced by sparse polymer ribbons with surface relief gratings.

    PubMed

    Ji, Zhichao; Zhang, Xinzheng; Shi, Bin; Li, Wei; Luo, Weiwei; Drevensek-Olenik, Irena; Wu, Qiang; Xu, Jingjun

    2016-01-15

    We report on the liquid crystal (LC) alignment induced by sparse polymer ribbons fabricated by the two-photon polymerization-based direct laser writing method. Each ribbon is fabricated by a single scan of the laser through the photoresist and possesses surface relief gratings on both sides. The relief gratings are caused by the optical interference between the incident and reflected laser beams. With the aid of these relief gratings, LC molecules can be well aligned along the selected direction of the ribbons. LC cells with the Z-shaped and checkerboard-type microstructures are constructed based on the sparse out-of-plane polymeric ribbons. Our results show that with such polymer ribbons a compartmentalized LC alignment in the arbitrary microstructures can be realized. PMID:26766708

  10. Ultrasensitive quantification of TAP-dependent antigen compartmentalization in scarce primary immune cell subsets

    PubMed Central

    Fischbach, Hanna; Döring, Marius; Nikles, Daphne; Lehnert, Elisa; Baldauf, Christoph; Kalinke, Ulrich; Tampé, Robert

    2015-01-01

    Presentation of peptides on major histocompatibility complex class I (MHC I) is essential for the establishment and maintenance of self-tolerance, priming of antigen-specific CD8+ T cells and the exertion of several T-cell effector functions. Cytosolic proteasomes continuously degrade proteins into peptides, which are actively transported across the endoplasmic reticulum (ER) membrane by the transporter associated with antigen processing (TAP). In the ER lumen antigenic peptides are loaded onto MHC I, which is displayed on the cell surface. Here we describe an innovative flow cytometric approach to monitor time-resolved ER compartmentalization of antigenic peptides. This assay allows the analysis of distinct primary human immune cell subsets at reporter peptide concentrations of 1 nM. Thus, this ultrasensitive method for the first time permits quantification of TAP activity under close to physiological conditions in scarce primary cell subsets such as antigen cross-presenting dendritic cells. PMID:25656091

  11. Information Processing in Single Cells and Small Networks: Insights from Compartmental Models

    NASA Astrophysics Data System (ADS)

    Poirazi, Panayiota

    2009-03-01

    The goal of this paper is to present a set of predictions generated by detailed compartmental models regarding the ways in which information may be processed, encoded and propagated by single cells and neural assemblies. Towards this goal, I will review a number of modelling studies from our lab that investigate how single pyramidal neurons and small neural networks in different brain regions process incoming signals that are associated with learning and memory. I will first discuss the computational capabilities of individual pyramidal neurons in the hippocampus [1-3] and how these properties may allow a single cell to discriminate between different memories [4]. I will then present biophysical models of prefrontal layer V neurons and small networks that exhibit sustained activity under realistic synaptic stimulation and discuss their potential role in working memory [5].

  12. Subcellular Compartmentalization and Trafficking of the Biosynthetic Machinery for Fungal Melanin.

    PubMed

    Upadhyay, Srijana; Xu, Xinping; Lowry, David; Jackson, Jennifer C; Roberson, Robert W; Lin, Xiaorong

    2016-03-22

    Protection by melanin depends on its subcellular location. Although most filamentous fungi synthesize melanin via a polyketide synthase pathway, where and how melanin biosynthesis occurs and how it is deposited as extracellular granules remain elusive. Using a forward genetic screen in the pathogen Aspergillus fumigatus, we find that mutations in an endosomal sorting nexin abolish melanin cell-wall deposition. We find that all enzymes involved in the early steps of melanin biosynthesis are recruited to endosomes through a non-conventional secretory pathway. In contrast, late melanin enzymes accumulate in the cell wall. Such subcellular compartmentalization of the melanin biosynthetic machinery occurs in both A. fumigatus and A. nidulans. Thus, fungal melanin biosynthesis appears to be initiated in endosomes with exocytosis leading to melanin extracellular deposition, much like the synthesis and trafficking of mammalian melanin in endosomally derived melanosomes. PMID:26972005

  13. Compartmentalization of gypsum and halite associated with cyanobacteria in saline soil crusts.

    PubMed

    Canfora, Loredana; Vendramin, Elisa; Vittori Antisari, Livia; Lo Papa, Giuseppe; Dazzi, Carmelo; Benedetti, Anna; Iavazzo, Pietro; Adamo, Paola; Jungblut, Anne D; Pinzari, Flavia

    2016-06-01

    The interface between biological and geochemical components in the surface crust of a saline soil was investigated using X-ray diffraction, and variable pressure scanning electron microscopy in combination with energy dispersive X-ray spectrometry. Mineral compounds such as halite and gypsum were identified crystallized around filaments of cyanobacteria. A total of 92 genera were identified from the bacterial community based on 16S gene pyrosequencing analysis. The occurrence of the gypsum crystals, their shapes and compartmentalization suggested that they separated NaCl from the immediate microenvironment of the cyanobacteria, and that some cyanobacteria and communities of sulfur bacteria may had a physical control over the distinctive halite and gypsum structures produced. This suggests that cyanobacteria might directly or indirectly promote the formation of a protective envelope made of calcium and sulfur-based compounds. PMID:27090760

  14. Spatial Compartmentalization Specializes the Function of Aurora A and Aurora B*

    PubMed Central

    Li, Si; Deng, Zhaoxuan; Fu, Jingyan; Xu, Caiyue; Xin, Guangwei; Wu, Zhige; Luo, Jia; Wang, Gang; Zhang, Shuli; Zhang, Boyan; Zou, Fangdong; Jiang, Qing; Zhang, Chuanmao

    2015-01-01

    Aurora kinase A and B share great similarity in sequences, structures, and phosphorylation motif, yet they show different localizations and play distinct crucial roles. The factors that determine such differences are largely unknown. Here we targeted Aurora A to the localization of Aurora B and found that Aurora A phosphorylates the substrate of Aurora B and substitutes its function in spindle checkpoint. In return, the centrosome targeting of Aurora B substitutes the function of Aurora A in the mitotic entry. Expressing the chimera proteins of the Auroras with exchanged N termini in cells indicates that the divergent N termini are also important for their spatiotemporal localizations and functions. Collectively, we demonstrate that functional divergence of Aurora kinases is determined by spatial compartmentalization, and their divergent N termini also contribute to their spatial and functional differentiation. PMID:25987563

  15. Spatial Compartmentalization Specializes the Function of Aurora A and Aurora B.

    PubMed

    Li, Si; Deng, Zhaoxuan; Fu, Jingyan; Xu, Caiyue; Xin, Guangwei; Wu, Zhige; Luo, Jia; Wang, Gang; Zhang, Shuli; Zhang, Boyan; Zou, Fangdong; Jiang, Qing; Zhang, Chuanmao

    2015-07-10

    Aurora kinase A and B share great similarity in sequences, structures, and phosphorylation motif, yet they show different localizations and play distinct crucial roles. The factors that determine such differences are largely unknown. Here we targeted Aurora A to the localization of Aurora B and found that Aurora A phosphorylates the substrate of Aurora B and substitutes its function in spindle checkpoint. In return, the centrosome targeting of Aurora B substitutes the function of Aurora A in the mitotic entry. Expressing the chimera proteins of the Auroras with exchanged N termini in cells indicates that the divergent N termini are also important for their spatiotemporal localizations and functions. Collectively, we demonstrate that functional divergence of Aurora kinases is determined by spatial compartmentalization, and their divergent N termini also contribute to their spatial and functional differentiation. PMID:25987563

  16. Compartmentalization of metabolic pathways in yeast mitochondria improves production of branched chain alcohols

    PubMed Central

    Avalos, José L.; Fink, Gerald R.; Stephanopoulos, Gregory

    2013-01-01

    Efforts to improve the production of a compound of interest in Saccharomyces cerevisiae have mainly involved engineering or overexpression of cytoplasmic enzymes. We show that targeted expression of metabolic pathways to mitochondria can increase production levels compared with expression of the same pathways in the cytoplasm. Compartmentalisation of the Ehrlich pathway into mitochondria increased isobutanol production by 260%, whereas overexpression of the same pathway in the cytoplasm only improved yields by 10%, compared with a strain overexpressing only the first three steps of the biosynthetic pathway. Subcellular fractionation of engineered strains reveals that targeting the enzymes of the Ehrlich pathway to the mitochondria achieves higher local enzyme concentrations. Other benefits of compartmentalization may include increased availability of intermediates, removing the need to transport intermediates out of the mitochondrion, and reducing the loss of intermediates to competing pathways. PMID:23417095

  17. The planar cell polarity protein Vangl2 is involved in postsynaptic compartmentalization.

    PubMed

    Nagaoka, Tadahiro; Kishi, Masashi

    2016-01-26

    The excitatory postsynaptic region of the vertebrate hippocampus is usually compartmentalized into the postsynaptic density (PSD) and N-cadherin-rich domain, which is important for synaptic adhesion. However, the molecular mechanisms underlying the compartment formation are unknown. In the present report, we show that the planar cell polarity (PCP) protein Van Gogh-like 2 (Vangl2) plays a role in this regionalization. In cultured rat hippocampal neurons that were subjected to Vangl2 expression silencing, the formed clusters of PSD-95, one of the major scaffolding proteins in PSD, tended to overlap with those of N-cadherin. Further, in the dendrites of these neurons, the immunofluorescence of PSD-95 was to some extent diffused, without a significant change in the total signal. Because Vangl2 physically interacts with both PSD-95 and N-cadherin in vivo, these results suggest that a PCP-related direct molecular mechanism underlies the horizontal polarization of the postsynaptic regions. PMID:26683906

  18. Engineering of customized meganucleases via in vitro compartmentalization and in cellulo optimization

    PubMed Central

    Takeuchi, Ryo; Choi, Michael; Stoddard, Barry L.

    2015-01-01

    Summary LAGLIDADG homing endonucleases (also referred to as ‘meganucleases’) are compact DNA cleaving enzymes that specifically recognize long target sequences (approximately 20 base pairs), and thus serve as useful tools for therapeutic genome engineering. While stand-alone meganucleases are sufficiently active to introduce targeted genome modification, they can be fused to additional sequence-specific DNA binding domains in order to improve their performance in target cells. In this chapter, we describe an approach to retarget meganucleases to DNA targets of interest (such as sequences found in genes and cis regulatory regions), which is feasible in an academic laboratory environment. A combination of two selection systems, in vitro compartmentalization and two-plasmid cleavage assay in bacteria, allow for efficient engineering of meganucleases that specifically cleave a wide variety of DNA sequences. PMID:25408403

  19. A self-compartmentalizing hexamer serine protease from Pyrococcus horikoshii: substrate selection achieved through multimerization.

    PubMed

    Menyhárd, Dóra K; Kiss-Szemán, Anna; Tichy-Rács, Éva; Hornung, Balázs; Rádi, Krisztina; Szeltner, Zoltán; Domokos, Klarissza; Szamosi, Ilona; Náray-Szabó, Gábor; Polgár, László; Harmat, Veronika

    2013-06-14

    Oligopeptidases impose a size limitation on their substrates, the mechanism of which has long been under debate. Here we present the structure of a hexameric serine protease, an oligopeptidase from Pyrococcus horikoshii (PhAAP), revealing a complex, self-compartmentalized inner space, where substrates may access the monomer active sites passing through a double-gated "check-in" system, first passing through a pore on the hexamer surface and then turning to enter through an even smaller opening at the monomers' domain interface. This substrate screening strategy is unique within the family. We found that among oligopeptidases, a residue of the catalytic apparatus is positioned near an amylogenic β-edge, which needs to be protected to prevent aggregation, and we found that different oligopeptidases use different strategies to achieve such an end. We propose that self-assembly within the family results in characteristically different substrate selection mechanisms coupled to different multimerization states. PMID:23632025

  20. Cellular compartmentation of cadmium and zinc in relation to other elements in the hyperaccumulator Arabidopsis halleri.

    PubMed

    Küpper, H; Lombi, E; Zhao, F J; McGrath, S P

    2000-12-01

    The cellular compartmentation of elements was analysed in the Zn hyperaccumulator Arabidopsis halleri (L.) O'Kane & Al-Shehbaz (=Cardaminopsis halleri) using energy-dispersive X-ray microanalysis of frozen-hydrated tissues. Quantitative data were obtained using oxygen as an internal standard in the analyses of vacuoles, whereas a peak/background ratio method was used for quantification of elements in pollen and dehydrated trichomes. Arabidopsis halleri was found to hyperaccumulate not only Zn but also Cd in the shoot biomass. While large concentrations of Zn and Cd were found in the leaves and roots, flowers contained very little. In roots grown hydroponically, Zn and Cd accumulated in the cell wall of the rhizodermis (root epidermis), mainly due to precipitation of Zn/Cd phosphates. In leaves, the trichomes had by far the largest concentrations of Zn and Cd. Inside the trichomes there was a striking sub-cellular compartmentation, with almost all the Zn and Cd being accumulated in a narrow ring in the trichome base. This distribution pattern was very different from that for Ca and P. The epidermal cells other than trichomes were very small and contained lower concentrations of Zn and Cd than mesophyll cells. In particular, the concentrations of Cd and Zn in the mesophyll cells increased markedly in response to increasing Zn and Cd concentrations in the nutrient solution. This indicates that the mesophyll cells in the leaves of A. halleri are the major storage site for Zn and Cd, and play an important role in their hyperaccumulation. PMID:11219586

  1. Compartmental distribution of GABAB receptor-mediated currents along the somatodendritic axis of hippocampal principal cells

    PubMed Central

    Degro, Claudius E.; Kulik, Akos; Booker, Sam A.; Vida, Imre

    2015-01-01

    Activity of cortical principal cells is controlled by the GABAergic system providing inhibition in a compartmentalized manner along their somatodendritic axis. While GABAAR-mediated inhibitory synaptic transmission has been extensively characterized in hippocampal principal cells, little is known about the distribution of postsynaptic effects of GABABRs. In the present study, we have investigated the functional localization of GABABRs and their effector inwardly rectifying potassium (Kir3) channels by combining electrophysiological recordings in acute rat hippocampal slices, high-resolution immunoelectron microscopic analysis and single cell simulations. Pharmacologically isolated slow inhibitory postsynaptic currents were elicited in the three major hippocampal principal cell types by endogenous GABA released by electrical stimulation, photolysis of caged-GABA, as well as the canonical agonist baclofen, with the highest amplitudes observed in the CA3. Spatially restricted currents were assessed along the axis of principal cells by uncaging GABA in the different hippocampal layers. GABABR-mediated currents were present along the entire somatodendritic axis of principal cells, but non-uniformly distributed: largest currents and the highest conductance densities determined in the simulations were consistently found on the distal apical dendrites. Finally, immunocytochemical localization of GABABRs and Kir3 channels showed that distributions overlap but their densities diverge, particularly on the basal dendrites of pyramidal cells. GABABRs current amplitudes and the conductance densities correlated better with Kir3 density, suggesting a bottlenecking effect defined by the effector channel. These data demonstrate a compartmentalized distribution of the GABABR-Kir3 signaling cascade and suggest differential control of synaptic transmission, dendritic integration and synaptic plasticity at afferent pathways onto hippocampal principal cells. PMID:25852540

  2. Pathway Compartmentalization in Peroxisome of Saccharomyces cerevisiae to Produce Versatile Medium Chain Fatty Alcohols

    PubMed Central

    Sheng, Jiayuan; Stevens, Joseph; Feng, Xueyang

    2016-01-01

    Fatty alcohols are value-added chemicals and important components of a variety of industries, which have a >3 billion-dollar global market annually. Long chain fatty alcohols (>C12) are mainly used in surfactants, lubricants, detergents, pharmaceuticals and cosmetics while medium chain fatty alcohols (C6–C12) could be used as diesel-like biofuels. Microbial production of fatty alcohols from renewable feedstock stands as a promising strategy to enable sustainable supply of fatty alcohols. In this study, we report, for the first time, that medium chain fatty alcohols could be produced in yeast via targeted expression of a fatty acyl-CoA reductase (TaFAR) in the peroxisome of Saccharomyces cerevisiae. By tagging TaFAR enzyme with peroxisomal targeting signal peptides, the TaFAR could be compartmentalized into the matrix of the peroxisome to hijack the medium chain fatty acyl-CoA generated from the beta-oxidation pathway and convert them to versatile medium chain fatty alcohols (C10 & C12). The overexpression of genes encoding PEX7 and acetyl-CoA carboxylase further improved fatty alcohol production by 1.4-fold. After medium optimization in fed-batch fermentation using glucose as the sole carbon source, fatty alcohols were produced at 1.3 g/L, including 6.9% 1-decanol, 27.5% 1-dodecanol, 2.9% 1-tetradecanol and 62.7% 1-hexadecanol. This work revealed that peroxisome could be engineered as a compartmentalized organelle for producing fatty acid-derived chemicals in S. cerevisiae. PMID:27230732

  3. Subcellular Compartmentation of the Diterpene Carnosic Acid and Its Derivatives in the Leaves of Rosemary1

    PubMed Central

    Munné-Bosch, Sergi; Alegre, Leonor

    2001-01-01

    The potent antioxidant properties of rosemary (Rosmarinus officinalis) extracts have been attributed to its major diterpene, carnosic acid. Carnosic acid has received considerable attention in food science and biomedicine, but little is known about its function in the plant in vivo. We recently found that highly oxidized diterpenes increase in rosemary plants exposed to drought and high light stress as a result of the antioxidant activity of carnosic acid (S. Munné-Bosch, K. Schwarz, L. Alegre [1999] Plant Physiol 121: 1047–1052). To elucidate the significance of the antioxidant function of carnosic acid in vivo we measured the relative amounts of carnosic acid and its metabolites in different compartments of rosemary leaves. Subcellular localization studies show that carnosic acid protects chloroplasts from oxidative stress in vivo by following a highly regulated compartmentation of oxidation products. Carnosic acid scavenges free radicals within the chloroplasts, giving rise to diterpene alcohols, mainly isorosmanol. This oxidation product is O-methylated within the chloroplasts, and the resulting form, 11,12-di-O-methylisorosmanol, is transferred to the plasma membrane. This appears to represent a mechanism of a way out for free radicals from chloroplasts. Carnosic acid also undergoes direct O-methylation within the chloroplasts, and its derived product, 12-O-methylcarnosic acid, accumulates in the plasma membrane. O-methylated diterpenes do not display antioxidant activity, but they may influence the stability of the plasma membrane. This study shows the relevance of the compartmentation of carnosic acid metabolism to the protection of rosemary plants from oxidative stress in vivo. PMID:11161064

  4. Probabilistic geomechanical analysis of compartmentalization at the Snøhvit CO2 sequestration project

    NASA Astrophysics Data System (ADS)

    Chiaramonte, Laura; White, Joshua A.; Trainor-Guitton, Whitney

    2015-02-01

    Pressure buildup caused by large-scale CO2 injection is a key concern during a carbon sequestration project. Large overpressures can compromise seal integrity, reactivate faults, and induce seismicity. Furthermore, pressure buildup is directly related with storage capacity. In this work we study the geomechanical response to CO2 injection at Snøhvit, to understand the potential for fault reactivation, leakage, and contamination of the producing interval through bounding faults. Furthermore, we evaluate the potential contribution of a structural component to reservoir compartmentalization. We combine simplified analytical models, based on critically stressed fracture theory and a Mohr-Coulomb failure criterion, with a rigorous sensitivity analysis. Large stress uncertainties are present and reflected in the modeling results. It was found that under the most likely stress state the faults are fairly stable and caprock hydrofracturing would be expected before fault reactivation. In most of the analyzed cases, the critical pressure perturbation needed for reactivation is above 13 MPa, which was the limiting pressure increase before reaching the fracture pressure. Faults were found to be ~ 20% less stable when considering variations in SHmax orientation. In those cases, fault reactivation could be expected before caprock failure if injection continued. However, if the pressure increase did reach the critical values for seal failure estimated under the worst case (and least likely) stress state, no indication of such failure can be observed in the measured pressure response. Finally, the potential role of a structural component in the compartmentalization and fluid migration is difficult to assess due to the stress state uncertainty.

  5. The role of the bi-compartmental stem cell niche in delaying cancer

    NASA Astrophysics Data System (ADS)

    Shahriyari, Leili; Komarova, Natalia L.

    2015-10-01

    In recent years, by using modern imaging techniques, scientists have found evidence of collaboration between different types of stem cells (SCs), and proposed a bi-compartmental organization of the SC niche. Here we create a class of stochastic models to simulate the dynamics of such a heterogeneous SC niche. We consider two SC groups: the border compartment, S1, is in direct contact with transit-amplifying (TA) cells, and the central compartment, S2, is hierarchically upstream from S1. The S1 SCs differentiate or divide asymmetrically when the tissue needs TA cells. Both groups proliferate when the tissue requires SCs (thus maintaining homeostasis). There is an influx of S2 cells into the border compartment, either by migration, or by proliferation. We examine this model in the context of double-hit mutant generation, which is a rate-limiting step in the development of many cancers. We discover that this type of a cooperative pattern in the stem niche with two compartments leads to a significantly smaller rate of double-hit mutant production compared with a homogeneous, one-compartmental SC niche. Furthermore, the minimum probability of double-hit mutant generation corresponds to purely symmetric division of SCs, consistent with the literature. Finally, the optimal architecture (which minimizes the rate of double-hit mutant production) requires a large proliferation rate of S1 cells along with a small, but non-zero, proliferation rate of S2 cells. This result is remarkably similar to the niche structure described recently by several authors, where one of the two SC compartments was found more actively engaged in tissue homeostasis and turnover, while the other was characterized by higher levels of quiescence (but contributed strongly to injury recovery). Both numerical and analytical results are presented.

  6. Consequences of plant invasions on compartmentalization and species' roles in plant-pollinator networks.

    PubMed

    Albrecht, Matthias; Padrón, Benigno; Bartomeus, Ignasi; Traveset, Anna

    2014-08-01

    Compartmentalization-the organization of ecological interaction networks into subsets of species that do not interact with other subsets (true compartments) or interact more frequently among themselves than with other species (modules)-has been identified as a key property for the functioning, stability and evolution of ecological communities. Invasions by entomophilous invasive plants may profoundly alter the way interaction networks are compartmentalized. We analysed a comprehensive dataset of 40 paired plant-pollinator networks (invaded versus uninvaded) to test this hypothesis. We show that invasive plants have higher generalization levels with respect to their pollinators than natives. The consequences for network topology are that-rather than displacing native species from the network-plant invaders attracting pollinators into invaded modules tend to play new important topological roles (i.e. network hubs, module hubs and connectors) and cause role shifts in native species, creating larger modules that are more connected among each other. While the number of true compartments was lower in invaded compared with uninvaded networks, the effect of invasion on modularity was contingent on the study system. Interestingly, the generalization level of the invasive plants partially explains this pattern, with more generalized invaders contributing to a lower modularity. Our findings indicate that the altered interaction structure of invaded networks makes them more robust against simulated random secondary species extinctions, but more vulnerable when the typically highly connected invasive plants go extinct first. The consequences and pathways by which biological invasions alter the interaction structure of plant-pollinator communities highlighted in this study may have important dynamical and functional implications, for example, by influencing multi-species reciprocal selection regimes and coevolutionary processes. PMID:24943368

  7. Polyamine/Nucleotide Coacervates Provide Strong Compartmentalization of Mg²⁺, Nucleotides, and RNA.

    PubMed

    Frankel, Erica A; Bevilacqua, Philip C; Keating, Christine D

    2016-03-01

    Phase separation of aqueous solutions containing polyelectrolytes can lead to formation of dense, solute-rich liquid droplets referred to as coacervates, surrounded by a dilute continuous phase of much larger volume. This type of liquid-liquid phase separation is thought to help explain the appearance of polyelectrolyte-rich intracellular droplets in the cytoplasm and nucleoplasm of extant biological cells and may be relevant to protocellular compartmentalization of nucleic acids on the early Earth. Here we describe complex coacervates formed upon mixing the polycation poly(allylamine) (PAH, 15 kDa) with the anionic nucleotides adenosine 5'-mono-, di-, and triphosphate (AMP, ADP, and ATP). Droplet formation was observed over a wide range of pH and MgCl2 concentrations. The nucleotides themselves as well as Mg(2+) and RNA oligonucleotides were all extremely concentrated within the coacervates. Nucleotides present at just 2.5 mM in bulk solution had concentrations greater than 1 M inside the coacervate droplets. A solution with a total Mg(2+) concentration of 10 mM had 1-5 M Mg(2+) in the coacervates, and RNA random sequence (N54) partitioned ∼10,000-fold into the coacervates. Coacervate droplets are thus rich in nucleotides, Mg(2+), and RNA, providing a medium favorable for generating functional RNAs. Compartmentalization of nucleotides at high concentrations could have facilitated their polymerization to form oligonucleotides, which preferentially accumulate in the droplets. Locally high Mg(2+) concentrations could have aided folding and catalysis in an RNA world, making coacervate droplets an appealing platform for exploring protocellular environments. PMID:26844692

  8. Caveolin-3 regulates compartmentation of cardiomyocyte beta2-adrenergic receptor-mediated cAMP signaling.

    PubMed

    Wright, Peter T; Nikolaev, Viacheslav O; O'Hara, Thomas; Diakonov, Ivan; Bhargava, Anamika; Tokar, Sergiy; Schobesberger, Sophie; Shevchuk, Andrew I; Sikkel, Markus B; Wilkinson, Ross; Trayanova, Natalia A; Lyon, Alexander R; Harding, Sian E; Gorelik, Julia

    2014-02-01

    The purpose of this study was to investigate whether caveolin-3 (Cav3) regulates localization of β2-adrenergic receptor (β2AR) and its cAMP signaling in healthy or failing cardiomyocytes. We co-expressed wildtype Cav3 or its dominant-negative mutant (Cav3DN) together with the Förster resonance energy transfer (FRET)-based cAMP sensor Epac2-camps in adult rat ventricular myocytes (ARVMs). FRET and scanning ion conductance microscopy were used to locally stimulate β2AR and to measure cytosolic cAMP. Cav3 overexpression increased the number of caveolae and decreased the magnitude of β2AR-cAMP signal. Conversely, Cav3DN expression resulted in an increased β2AR-cAMP response without altering the whole-cell L-type calcium current. Following local stimulation of Cav3DN-expressing ARVMs, β2AR response could only be generated in T-tubules. However, the normally compartmentalized β2AR-cAMP signal became diffuse, similar to the situation observed in heart failure. Finally, overexpression of Cav3 in failing myocytes led to partial β2AR redistribution back into the T-tubules. In conclusion, Cav3 plays a crucial role for the localization of β2AR and compartmentation of β2AR-cAMP signaling to the T-tubules of healthy ARVMs, and overexpression of Cav3 in failing myocytes can partially restore the disrupted localization of these receptors. PMID:24345421

  9. Caveolin-3 regulates compartmentation of cardiomyocyte beta2-adrenergic receptor-mediated cAMP signaling

    PubMed Central

    Wright, Peter T.; Nikolaev, Viacheslav O.; O’Hara, Thomas; Diakonov, Ivan; Bhargava, Anamika; Tokar, Sergiy; Schobesberger, Sophie; Shevchuk, Andrew I.; Sikkel, Markus B.; Wilkinson, Ross; Trayanova, Natalia A.; Lyon, Alexander R.; Harding, Sian E.; Gorelik, Julia

    2014-01-01

    The purpose of this study was to investigate whether caveolin-3 (Cav3) regulates localization of β2-adrenergic receptor (β2AR) and its cAMP signaling in healthy or failing cardiomyocytes. We co-expressed wildtype Cav3 or its dominant-negative mutant (Cav3DN) together with the Förster resonance energy transfer (FRET)-based cAMP sensor Epac2-camps in adult rat ventricular myocytes (ARVMs). FRET and scanning ion conductance microscopy were used to locally stimulate β2AR and to measure cytosolic cAMP. Cav3 overexpression increased the number of caveolae and decreased the magnitude of β2AR-cAMP signal. Conversely, Cav3DN expression resulted in an increased β2AR-cAMP response without altering the whole-cell L-type calcium current. Following local stimulation of Cav3DN-expressing ARVMs, β2AR response could only be generated in T-tubules. However, the normally compartmentalized β2AR-cAMP signal became diffuse, similar to the situation observed in heart failure. Finally, overexpression of Cav3 in failing myocytes led to partial β2AR redistribution back into the T-tubules. In conclusion, Cav3 plays a crucial role for the localization of β2AR and compartmentation of β2AR-cAMP signaling to the T-tubules of healthy ARVMs, and overexpression of Cav3 in failing myocytes can partially restore the disrupted localization of these receptors. PMID:24345421

  10. PKA Compartmentalization via AKAP220 and AKAP12 Contributes to Endothelial Barrier Regulation

    PubMed Central

    Radeva, Mariya Y.; Kugelmann, Daniela; Spindler, Volker; Waschke, Jens

    2014-01-01

    cAMP-mediated PKA signaling is the main known pathway involved in maintenance of the endothelial barrier. Tight regulation of PKA function can be achieved by discrete compartmentalization of the enzyme via physical interaction with A-kinase anchoring proteins (AKAPs). Here, we investigated the role of AKAPs 220 and 12 in endothelial barrier regulation. Analysis of human and mouse microvascular endothelial cells as well as isolated rat mesenteric microvessels was performed using TAT-Ahx-AKAPis peptide, designed to competitively inhibit PKA-AKAP interaction. In vivo microvessel hydraulic conductivity and in vitro transendothelial electrical resistance measurements showed that this peptide destabilized endothelial barrier properties, and dampened the cAMP-mediated endothelial barrier stabilization induced by forskolin and rolipram. Immunofluorescence analysis revealed that TAT-Ahx-AKAPis led to both adherens junctions and actin cytoskeleton reorganization. Those effects were paralleled by redistribution of PKA and Rac1 from endothelial junctions and by Rac1 inactivation. Similarly, membrane localization of AKAP220 was also reduced. In addition, depletion of either AKAP12 or AKAP220 significantly impaired endothelial barrier function and AKAP12 was also shown to interfere with cAMP-mediated barrier enhancement. Furthermore, immunoprecipitation analysis demonstrated that AKAP220 interacts not only with PKA but also with VE-cadherin and ß-catenin. Taken together, these results indicate that AKAP-mediated PKA subcellular compartmentalization is involved in endothelial barrier regulation. More specifically, AKAP220 and AKAP12 contribute to endothelial barrier function and AKAP12 is required for cAMP-mediated barrier stabilization. PMID:25188285

  11. Bioaccessibility of selenium after human ingestion in relation to its chemical species and compartmentalization in maize.

    PubMed

    Mombo, Stéphane; Schreck, Eva; Dumat, Camille; Laplanche, Christophe; Pierart, Antoine; Longchamp, Mélanie; Besson, Philippe; Castrec-Rouelle, Maryse

    2016-06-01

    Selenium is a micronutrient needed by all living organisms including humans, but often present in low concentration in food with possible deficiency. From another side, at higher concentrations in soils as observed in seleniferous regions of the world, and in function of its chemical species, Se can also induce (eco)toxicity. Root Se uptake was therefore studied in function of its initial form for maize (Zea mays L.), a plant widely cultivated for human and animal food over the world. Se phytotoxicity and compartmentalization were studied in different aerial plant tissues. For the first time, Se oral human bioaccessibility after ingestion was assessed for the main Se species (Se(IV) and Se(VI)) with the BARGE ex vivo test in maize seeds (consumed by humans), and in stems and leaves consumed by animals. Corn seedlings were cultivated in hydroponic conditions supplemented with 1 mg L(-1) of selenium (Se(IV), Se(VI), Control) for 4 months. Biomass, Se concentration, and bioaccessibility were measured on harvested plants. A reduction in plant biomass was observed under Se treatments compared to control, suggesting its phytotoxicity. This plant biomass reduction was higher for selenite species than selenate, and seed was the main affected compartment compared to control. Selenium compartmentalization study showed that for selenate species, a preferential accumulation was observed in leaves, whereas selenite translocation was very limited toward maize aerial parts, except in the seeds where selenite concentrations are generally high. Selenium oral bioaccessibility after ingestion fluctuated from 49 to 89 % according to the considered plant tissue and Se species. Whatever the tissue, selenate appeared as the most human bioaccessible form. A potential Se toxicity was highlighted for people living in seleniferous regions, this risk being enhanced by the high Se bioaccessibility. PMID:26387097

  12. Pathway Compartmentalization in Peroxisome of Saccharomyces cerevisiae to Produce Versatile Medium Chain Fatty Alcohols.

    PubMed

    Sheng, Jiayuan; Stevens, Joseph; Feng, Xueyang

    2016-01-01

    Fatty alcohols are value-added chemicals and important components of a variety of industries, which have a >3 billion-dollar global market annually. Long chain fatty alcohols (>C12) are mainly used in surfactants, lubricants, detergents, pharmaceuticals and cosmetics while medium chain fatty alcohols (C6-C12) could be used as diesel-like biofuels. Microbial production of fatty alcohols from renewable feedstock stands as a promising strategy to enable sustainable supply of fatty alcohols. In this study, we report, for the first time, that medium chain fatty alcohols could be produced in yeast via targeted expression of a fatty acyl-CoA reductase (TaFAR) in the peroxisome of Saccharomyces cerevisiae. By tagging TaFAR enzyme with peroxisomal targeting signal peptides, the TaFAR could be compartmentalized into the matrix of the peroxisome to hijack the medium chain fatty acyl-CoA generated from the beta-oxidation pathway and convert them to versatile medium chain fatty alcohols (C10 &C12). The overexpression of genes encoding PEX7 and acetyl-CoA carboxylase further improved fatty alcohol production by 1.4-fold. After medium optimization in fed-batch fermentation using glucose as the sole carbon source, fatty alcohols were produced at 1.3 g/L, including 6.9% 1-decanol, 27.5% 1-dodecanol, 2.9% 1-tetradecanol and 62.7% 1-hexadecanol. This work revealed that peroxisome could be engineered as a compartmentalized organelle for producing fatty acid-derived chemicals in S. cerevisiae. PMID:27230732

  13. HIV-1 Nef sequence and functional compartmentalization in the gut is not due to differential cytotoxic T lymphocyte selective pressure.

    PubMed

    Lewis, Martha J; Frohnen, Patricia; Ibarrondo, F Javier; Reed, Diane; Iyer, Varun; Ng, Hwee L; Elliott, Julie; Yang, Otto O; Anton, Peter

    2013-01-01

    The gut is the largest lymphoid organ in the body and a site of active HIV-1 replication and immune surveillance. The gut is a reservoir of persistent infection in some individuals with fully suppressed plasma viremia on combination antiretroviral therapy (cART) although the cause of this persistence is unknown. The HIV-1 accessory protein Nef contributes to persistence through multiple functions including immune evasion and increasing infectivity. Previous studies showed that Nef's function is shaped by cytotoxic T lymphocyte (CTL) responses and that there are distinct populations of Nef within tissue compartments. We asked whether Nef's sequence and/or function are compartmentalized in the gut and how compartmentalization relates to local CTL immune responses. Primary nef quasispecies from paired plasma and sigmoid colon biopsies from chronically infected subjects not on therapy were sequenced and cloned into Env(-) Vpu(-) pseudotyped reporter viruses. CTL responses were mapped by IFN-γ ELISpot using expanded CD8+ cells from blood and gut with pools of overlapping peptides covering the entire HIV proteome. CD4 and MHC Class I Nef-mediated downregulation was measured by flow cytometry. Multiple tests indicated compartmentalization of nef sequences in 5 of 8 subjects. There was also compartmentalization of function with MHC Class I downregulation relatively well preserved, but significant loss of CD4 downregulation specifically by gut quasispecies in 5 of 7 subjects. There was no compartmentalization of CTL responses in 6 of 8 subjects, and the selective pressure on quasispecies correlated with the magnitude CTL response regardless of location. These results demonstrate that Nef adapts via diverse pathways to local selective pressures within gut mucosa, which may be predominated by factors other than CTL responses such as target cell availability. The finding of a functionally distinct population within gut mucosa offers some insight into how HIV-1 may persist in

  14. Closing a gap in the nuclear envelope.

    PubMed

    Vietri, Marina; Stenmark, Harald; Campsteijn, Coen

    2016-06-01

    The nuclear envelope (NE) ensures nucleo-cytoplasmic compartmentalization, with trafficking of macromolecules across this double membrane controlled by embedded nuclear pore complexes (NPCs). The NE and associated proteins are dismantled during open mitosis and reestablishment of this barrier during mitotic exit requires dynamic remodeling of endoplasmic reticulum (ER) membranes and coordination with NPC reformation, with NPC deposition continuing during subsequent interphase. In this review, we discuss recent progress in our understanding of NE reformation and nuclear pore complex generation, with special focus on work implicating the endosomal sorting complex required for transport (ESCRT) membrane remodeling machinery in these events. PMID:27016712

  15. The paraveinal mesophyll of soybean leaves in relation to assimilate transfer and compartmentation : II. Structural, metabolic and compartmental changes during reproductive growth.

    PubMed

    Franceschi, V R; Giaquinta, R T

    1983-04-01

    Nitrogen and carbohydrate assimilates were temporally and spatially compartmented among various cell types in soybean (Glycine max L., Merr.) leaves during seed filling. The paraveinal mesophyll (PVM), a unique cell layer found in soybean, was demonstrated to function in the synthesis, compartmentation and remobilization of nitrogen reserves prior to and during the seed-filling stages. At anthesis, the PVM vacuoles contain substantial protein which completely disappears by two weeks into the seed filling. Distinct changes in the PVM cytoplasm, tonoplast and organelles were correlated with the presence or absence of the vacuolar material. Microautoradiography following the accumulation of several radiolabeled sugars and amino acids demonstrated the glycoprotein nature of the vacuolar material. Incorporation of methionine, leucine, glucose, and glucosamine resulted in heavy labelling of the PVM vacuole, in contrast to galactose, proline, and mannose which resulted in a much reduced labelling pattern. In addition, starch is unequally compartmented and degraded among the various leaf cells during seed filling. At the end of the photoperiod at the flowering stage, the highest starch accumulation was in the second palisade layer followed by the spongy mesophyll and the first (uppermost) palisade layer. Starch in the first palisade layer was completely degraded during the dark whereas the starch in the second palisade and spongy mesophyll was not remobilized to any appreciable extent. By mid-podfilling (approximately five weeks postanthesis) starch was absent in the first palisade layer at the end of the photoperiod while the second palisade and spongy mesophyll layers contained substantial starch. Starch was remobilized from these latter cells during the remainder of seed filling when current photosynthetic production is low. Structural changes associated with cell senescence first appear in the upper palisade layer and then progress (excluding the PVM) to the second

  16. Three-Dimensional Compartmentalization of Subsurface Ground Water Flow in Eastern North American Mesozoic Basins

    NASA Astrophysics Data System (ADS)

    Ryan, M. P.; Sutphin, D. M.; Daniels, D. L.; Pierce, H. A.; Smoot, J. P.

    2002-05-01

    An extensive network of diabase intrusions occurs in several of the largest Mesozoic basins of Eastern North America, including the Culpeper, Gettysburg, Newark, and Hartford basins. Within each, great dikes, inclined sheets, and lopoliths cut through the surrounding sandstones, siltstones, and conglomerates in ways that subdivide the regional subsurface flow field, and thus compartmentalize the basin. In the Culpeper basin, for example, the scale- and direction-dependent permeability of diabase spans the range 10-17 to 10-21 m2, whereas the permeability of the heavily fractured sediments is in the range 10-12 to 10-14 m2. Thus there is at least three, and upwards of nine, orders of magnitude difference in permeability between the diabase and the surrounding sediments. This great permeability contrast is at the heart of basin compartmentalization and the related subsurface hydrologic phenomena. In the Culpeper basin, our understanding of compartmentalization is guided by the following geological, geophysical, and hydrologic measurements and observations: (1) Short wavelength aeromagnetic anomalies constrain the geometry of the up-turned margins of diabase lopoliths. These lopoliths bound compartments horizontally and vertically; (2) Deep compartment structure has been resolved to 800 meters by in-situ AudioMagnetotelluric experiments; (3) Alignments of hornfels-hosted springs parallel to the diabase-hornfels contact along a compartment wall. We posit that eastward-migrating ground water is forced up and out to the surface when it comes into contact with the low permeability diabase at depth; (4) Direct observations of high fluid flow from bedding plane fractures within hornfels in the diabase-hornfels contact ``no-flow boundary condition'' region of a compartment's walls; (5) Direct drilling into and through a compartment's margins. Pumping yields within diabase are ~2 gal./min., whereas penetration of the compartment margins (drilling from diabase into the

  17. Engineering nanostructured polymer blends with controlled nanoparticle location for excellent microwave absorption: a compartmentalized approach.

    PubMed

    Biswas, Sourav; Kar, Goutam Prasanna; Bose, Suryasarathi

    2015-07-14

    In order to obtain better materials, control over the precise location of nanoparticles is indispensable. It is shown here that ordered arrangements of nanoparticles, possessing different characteristics (electrical/magnetic dipoles), in the blend structure can result in excellent microwave absorption. This is manifested from a high reflection loss of ca. -67 dB for the best blend structure designed here. To attenuate electromagnetic radiation, the key parameters of high electrical conductivity and large dielectric/magnetic loss are targeted here by including a conductive material [multiwall carbon nanotubes, MWNTs], ferroelectric nanostructured material with associated relaxations in the GHz frequency [barium titanate, BT] and lossy ferromagnetic nanoparticles [nickel ferrite, NF]. In this study, bi-continuous structures were designed using 50/50 (by wt) blends of polycarbonate (PC) and polyvinylidene fluoride (PVDF). The MWNTs were modified using an electron acceptor molecule, a derivative of perylenediimide, which facilitates π-π stacking with the nanotubes and stimulates efficient charge transport in the blends. The nanoscopic materials have specific affinity towards the PVDF phase. Hence, by introducing surface-active groups, an ordered arrangement can be tailored. To accomplish this, both BT and NF were first hydroxylated followed by the introduction of amine-terminal groups on the surface. The latter facilitated nucleophilic substitution reactions with PC and resulted in their precise location. In this study, we have shown for the first time that by a compartmentalized approach, superior EM attenuation can be achieved. For instance, when the nanoparticles were localized exclusively in the PVDF phase or in both the phases, the minimum reflection losses were ca. -18 dB (for the MWNT/BT mixture) and -29 dB (for the MWNT/NF mixture), and the shielding occurred primarily through reflection. Interestingly, by adopting the compartmentalized approach wherein the

  18. Compartmental modeling of PAH transport in soil column experiments under variably-saturated flow conditions

    NASA Astrophysics Data System (ADS)

    Sartori, F.; Sericano, J. L.; Wade, T. L.; Mohanty, B. P.

    2012-12-01

    Knowledge about the mobilization of polycyclic aromatic hydrocarbons (PAH) from PAH-laden soils or sediments is important to understand their bioavailability, and ultimately assess the environmental risk of PAH transport from surface soils into the groundwater. The transport and kinetics of three PAH from a spiked soil layer (2-3 cm soil depth), Phenanthrene-d10 (1900 ng/g), Naphthalene-d8 (1500 ng/g), and Pyrene-d10 (1800 ng/g), were investigated by performing a series of 8 rainfall events during 25 days in two large, replicate soil columns (length: 35 cm; diameter: 14.5 cm; 1 Pore Volume [PV]=2.29 L) under variably-saturated flow conditions. The water-methanol displacing solutions were at volumetric fractions of 0.3 and 0.6 during day 1 (E1) through E8 and E12-E22, respectively. Soil matric potential (h) was monitored at 5-cm and 20-cm depth and volumetric water content (θ) at 12.5-cm and 27.5-cm depth. Soil solution was sampled at 5 cm- (n=46) and 27.5-cm depth (n=46), and the effluent at the bottom of the column (n=163). HYDRUS-1D was used for inverse modeling of h and θ data and to predict θ at specific times and soil depth increments. First-order kinetics, compartmental models describing the transfer of PAH from the soil compartment to the soil solution compartment (desorption) and vice versa (sorption), were used to estimate mass transfer rates (φs, sorption; φd, desorption; φe, elimination), PAH mass in each compartment, and partition coefficients (Kd). Phenanthrene breakthrough curve could be interpreted through a two-parameter, two-compartment model corresponding to the common two-site sorption model, whose parameter estimates (and 95% confidence intervals) were φd=2.72 (2.31, 3.19) PV-1 and φe=4.67 (3.82, 5.7 ) PV-1. Naphthalene breakthrough curve followed a simple one-compartment elimination model, φe=2.0 (1.9, 2.1) PV-1, and that of Pyrene a three-parameter, two-compartment model, φs=0.0454 (0.00853, 0.0603) PV-1, φd=0.165 (0.0319, 0.855) PV

  19. Intracellular diffusion, binding, and compartmentalization of the fluorescent calcium indicators indo-1 and fura-2.

    PubMed Central

    Blatter, L. A.; Wier, W. G.

    1990-01-01

    We studied intracellular binding and possible compartmentalization of the fluorescent Ca2+ indicators, indo-1 and fura-2, in single mammalian cardiac ventricular cells that had been loaded with indo-1 and fura-2 by exposure to the acetoxymethylester form of the indicators (indo-1/AM and fura-2/AM). Techniques similar to those used in experiments on fluorescence recovery after photobleaching (FRAP) were used. It was assumed that reversible binding in myoplasm would be evident as slowed recovery of fluorescence after photobleaching, and that irreversible binding of the indicators to immobile myoplasmic sites (or "compartmentalization" in organelles) would be evident as incomplete recovery. Through the use of a mask, one half of a cell was exposed to high-intensity ultraviolet (UV) light to bleach the indo-1 or fura-2 in only that part of the cell. Upon removal of the mask and termination of the high-intensity UV illumination, fluorescence recovered in the bleached half of the cell, indicating diffusion of indo-1 and fura-2. Mathematical modeling of the diffusional redistribution of the indicators indicated that in these cells the apparent diffusion coefficient for indo-1 is 1.57 x 10(-7) cm2 s-1 (SD 0.48 x 10(-7) cm2 s-1; n = 5 cells, 21 degrees C), and for fura-2 is 3.19 x 10(-7) cm2 s-1 (SD 1.85 x 10(-7) cm2 s-1; n = 6 cells, 21 degrees C). These values are approximately 6 and 3, respectively, times smaller than those expected for free diffusion in the myoplasm. In the bleached half of the cell the recovered level of fluorescence never reached the final level in the half not exposed to UV light. The extent of incomplete recovery was variable amongst the cells. Our analysis indicated that, under the conditions we used, approximately one-third of the intracellular dye is not diffusible in the myoplasm. Images FIGURE 1 FIGURE 2 PMID:2275965

  20. Organization of the marmoset cerebellum in three-dimensional space: lobulation, aldolase C compartmentalization and axonal projection.

    PubMed

    Fujita, Hirofumi; Oh-Nishi, Arata; Obayashi, Shigeru; Sugihara, Izumi

    2010-05-15

    The cerebellar cortex is organized by transverse foliation and longitudinal compartmentalization. Although the latter, which is recognized through the molecular expression in subsets of Purkinje cells (PCs), is closely related to topographic axonal projection and represents functional divisions, the details have not been fully clarified in mammals other than rodents. Therefore, we examined folial and compartmental organization of the marmoset cerebellum, which resembles the macaque cerebellum, and compared it with that of the rodent cerebellum by aldolase C immunostaining, three-dimensional reconstruction of the PC layer, and labeling of olivocerebellar and corticonuclear projections. Longitudinal stripes of different aldolase C expression intensities separated the entire cerebellar cortex into multiple compartments. Lobule VIIAb-d was equivalent to rodent lobule VIc in that it contained a transverse gap in the cortical layers and served as the rostrocaudal boundary for compartments and axonal branching. Olivocortical and corticonuclear projection patterns in major compartments indicated that the compartmental organization in the marmoset cerebellum was generally equivalent to that in the rodent cerebellum, although two compartments were missing in the pars intermedia and several compartments that have not been seen in rodents were recognized in the flocculus, nodulus, and the most lateral hemisphere. Reconstruction showed that the paraflocculus and flocculus were formed by a single longitudinal sheet, the axis of which was parallel to the aldolase C compartments, PC dendrites, and olivocerebellar climbing fiber distribution. The results indicate that molecular compartmentalization in the marmoset cerebellum reflected both the common fundamental organization of the mammalian cerebellum and species-dependent differentiation. PMID:20235174

  1. Compartmental analysis of technetium-99m-teboroxime kinetics employing fast dynamic SPECT at rest and stress

    SciTech Connect

    Chiao, P.C.; Ficaro, E.P.; Dayaniki, F.

    1994-08-01

    The authors have examined the feasibility of compartmental analysis of {sup 99m}Tc-teboroxime kinetics in measuring physiological changes in response to adenosine-induced coronary vasodilation. To evaluate the effect of tracer recirculation on {sup 99m}Tc-teboroxime kinetics in the myocardium, they also compared compartmental analysis with washout analysis (monoexponertial fitting), which does not account for this effect. Eight healthy male volunteers were imaged using fast dynamic SPECT protocols (5 sec per tomographic image) at rest and during adenosine infusion. A two-compartment model was used and compartmental parameters K1 and k2 (characterizing the diffusion of {sup 99m}Tc-teboroxime from the blood to the myocardium and from the myocardium to the blood, respectively) were fitted from myocardial time-activity curves and left ventricular input functions. Both K1 and washout estimates for the whole left ventricular myocardium changed significantly in response to coronary vasodilation. Mean stress-to-rest (S/R) ratios were almost two times higher for K1 (S/R = 2.7 {plus_minus} 1.1) than for washout estimates (S/R = 1.5 {plus_minus} 0.3). Estimation of K1 for all local regions, except the septal wall, is feasible because variations in K1 estimates for all local regions, except the septum during stress, are comparable with those for the global region. The authors conclude that quantitative compartmental analysis of {sup 99m}Tc-teboroxime kinetics provides a sensitive indicator for changes in response to adenosine-induced coronary vasodilation. 39 refs., 7 figs., 1 tab.

  2. The association of HPV-16 seropositivity and natural immunity to reinfection: insights from compartmental models

    PubMed Central

    2013-01-01

    Background Seroreactivity, processes of seroconversion and seroreversion, in the context of HPV infection has been investigated in numerous studies. However, the data resulting from these studies are usually not accounted for in mathematical transmission models of various HPV types due to gaps in our understanding of the nature of seroreactivity and its implications for HPV natural history. Methods In this study we selected a number of simple but plausible compartmental transmission models of HPV-16, differing in assumptions regarding the relation between seropositivity and immunity, and attempted to calibrate them to Australian HPV seroprevalence data for females and males, as well as DNA prevalence data for females, using a Bayesian model comparison procedure. We ranked the models according to both their simplicity and ability to be fitted to the data. Results Our results demonstrate that models with seroreversion where seropositivity indicates only a partial or very short-term full protection against re-infection generate age-specific HPV DNA prevalence most consistent with the observed data when compared with other models. Conclusions Models supporting the notion that seropositive individuals are fully immune to reinfection demonstrated consistently inferior fits to the data than other models making no such assumption. PMID:23402400

  3. A bulk sub-femtoliter in vitro compartmentalization system using super-fine electrosprays.

    PubMed

    Sharma, Bineet; Takamura, Yuzuru; Shimoda, Tatsuya; Biyani, Manish

    2016-01-01

    The extreme miniaturization of biological and chemical assays in aqueous-droplet compartments enables spatiotemporal control for large-scale parallel experimentation and can thus permit new capabilities for "digitizing" directed molecular evolution methodologies. We report a remarkably facile bulk method to generate mega-scale monodisperse sub-femtoliter aqueous droplets by electrospray, using a prototype head with super-fine inkjet technology. Moreover, the electrostatic inkjet nozzle that injects the aqueous phase when immersed within an immiscible phase (an optimized oil/surfactant mixture) has the advantage of generating cell-like sub-femtoliter compartments for biomolecule encapsulation and successive biological and chemical reactions. Sub-femtoliter droplets of both liquid (water-in-oil, volumes ranging from 0.2 to 6.4 fL) and gel bead (agarose-in-oil, volume ranging from 0.3 to 15.6 fL) compartments with average sizes of 1.3 μm and 1.5 μm, respectively, were successfully generated using an inkjet nozzle at a speed of more than 10(5) droplets per second. We demonstrated the applicability of this system by synthesizing fluorescent proteins using a cell-free expression system inside electrosprayed sub-femtoliter droplets at an accelerated rate, thereby extending the utility of in vitro compartmentalization with improved analytical performance for a top-down artificial cellular system. PMID:27199080

  4. Bystander effects and compartmental stress response to X-ray irradiation in L929 cells.

    PubMed

    Temelie, Mihaela; Stroe, Daniela; Petcu, Ileana; Mustaciosu, Cosmin; Moisoi, Nicoleta; Savu, Diana

    2016-08-01

    Bystander effects are indirect consequences of radiation and many other stress factors. They occur in cells that are not directly exposed to these factors, but receive signals from affected cells either by gap junctions or by molecules released in the medium. Characterizing these effects and deciphering the underlying mechanisms involved in radiation-induced bystander effects are relevant for cancer radiotherapy and radioprotection. At doses of X-ray radiation 0.5 and 1 Gy, we detected bystander effects as increased numbers of micronuclei shortly after the treatment, through medium transfer and by co-cultures. Interestingly, bystander cells did not exhibit long-term adverse changes in viability. Evaluation of several compartmental stress markers (CHOP, BiP, mtHsp60, cytHsp70) by qRT-PCR did not reveal expression changes at transcriptional level. We investigated the involvement of ROS and NO in this process by addition of specific scavengers of these molecules, DMSO or c-PTIO in the transferred medium. This approach proved that ROS but not NO is involved in the induction of lesions in the acceptor cells. These results indicate that L929 cells are susceptible to stress effects of radiation-induced bystander signaling. PMID:27025606

  5. Compartmentalization and Ca2+ buffering are essential for prevention of light induced retinal degeneration

    PubMed Central

    Weiss, Shirley; Kohn, Elkana; Dadon, Daniela; Katz, Ben; Peters, Maximilian; Lebendiker, Mario; Kosloff, Mickey; Jo Colley, Nansi; Minke, Baruch

    2012-01-01

    Fly photoreceptors are polarized cells, which have an extended interface between their cell body and the light signaling compartment, the rhabdomere. Upon intense illumination, rhabdomeric calcium concentration reaches millimolar levels that would be toxic if Ca2+ diffusion between the rhabdomere and cell body was not robustly attenuated. Yet, it is not clear how such effective attenuation is obtained. Here we show that Ca2+ homeostasis in the photoreceptor cell relies on the protein calphotin. This unique protein functions as an immobile Ca2+ buffer, which is localized along the base of the rhabdomere, separating the signaling compartment from the cell body. Generation and analyses of transgenic Drosophila strains, in which calphotin expression levels were reduced in a graded manner, showed that moderately reduced calphotin expression impaired Ca2+ homeostasis while calphotin elimination resulted in severe light dependent photoreceptor degeneration. Electron microscopy, electrophysiology and optical methods revealed that the degeneration was rescued by prevention of Ca2+ overload via overexpression of CalX, the Na+-Ca2+ exchanger. In addition, Ca2+ imaging experiments showed that reduced calphotin levels resulted in abnormally fast kinetics of Ca2+elevation in photoreceptor cells. Together, the data suggest that calphotin functions as a Ca2+ buffer; a possibility which we directly demonstrate by expressing calphotin in a heterologous expression system. We propose that calphotin-mediated compartmentalization and Ca2+ buffering constitute an effective strategy to protect cells from Ca2+ overload and light induced degeneration. PMID:23077055

  6. Identification of HIV-1 Genitourinary Tract Compartmentalization by Analyzing the env Gene Sequences in Urine

    PubMed Central

    BLASI, Maria; CARPENTER, J. Harris; BALAKUMARAN, Bala; CARA, Andrea; GAO, Feng; KLOTMAN, Mary E.

    2015-01-01

    Objective HIV-1 persists indefinitely in memory CD4+ T cells and other long-lived cellular reservoirs despite antiretroviral therapy (ART). Our group had previously demonstrated that HIV-1 can establish a productive infection in renal epithelial cells and that the kidney represents a separate compartment for HIV-1 replication. Here, to better understand the viruses in this unique site, we genetically characterized and compared the viruses in blood and urine specimens from twenty-four HIV-1 infected subjects with detectable viremia. Design and Methods Blood and urine samples were obtained from 35 HIV-1 positive subjects. Single-genome amplification was performed on HIV-1 env RNA and DNA isolated from urine supernatants and urine derived cell pellets respectively, as well as from plasma and PBMC from the same individuals. Neighbor-joining trees were constructed under the Kimura 2-parameter mode. Results We amplified and sequenced the full-length HIV-1 envelope (env) gene from twelve of the twenty-four individuals, indicating that fifty percent (50%) of the viremic HIV-1 positive patients had viral RNA in their urine. Phylogenetic analysis of the env sequences from four subjects with more than fifteen urine-derived env sequences showed that the majority of the sequences from urine formed distinct cluster(s) independent of those PBMC and plasma-derived sequences, consistent with viral compartmentalization in the urine. Conclusions Our results suggest the presence of a distinct HIV compartment in the genitourinary tract. PMID:26372275

  7. Reservoir compartmentalization and management strategies: Lessons learned in the Illinois basin

    SciTech Connect

    Grube, J.P.; Crockett, J.E.; Huff, B.G.

    1997-08-01

    A research project jointly sponsored by the US Department of Energy and the Illinois State Geological Survey focused on the Cypress and Aux Vases Formations (Mississippian), major clastic reservoirs in the Illinois Basin. Results from the research showed that understanding the nature and distribution of reservoir compartments, and using effective reservoir management strategies, can significantly improve recovery efficiencies from oil fields in this mature basin. Compartments can be most effectively drained where they are geologically well defined and reservoir management practices are coordinated through unified, compartment-wide, development programs. Our studies showed that the Cypress and Aux Vases reservoirs contain lateral and vertical permeability barriers forming compartments that range in size from isolated, interlaminated sandstone and shale beds to sandstone bodies tens of feet in thickness and more than a mile in length. Stacked or shingled, genetically similar sandstone bodies are commonly separated by thin impermeable intervals that can be difficult to distinguish on logs and can, therefore, cause correlation problems, even between wells drilled on spacing of less than ten acres. Lateral separation of sandstone bodies causes similar problems. Reservoir compartmentalization reduces primary and particularly secondary recovery by trapping pockets of by-passed or banked oil. Compartments can be detected by comparing recovery factors of genetically similar sandstone bodies within a field; using packers to separate commingled intervals and analyzing fluid recoveries and pressures; making detailed core-to-log calibrations that identify compartment boundaries; and analyzing pressure data from waterflood programs.

  8. Modeling Heterogeneity in Direct Infectious Disease Transmission in a Compartmental Model

    PubMed Central

    Kong, Lingcai; Wang, Jinfeng; Han, Weiguo; Cao, Zhidong

    2016-01-01

    Mathematical models have been used to understand the transmission dynamics of infectious diseases and to assess the impact of intervention strategies. Traditional mathematical models usually assume a homogeneous mixing in the population, which is rarely the case in reality. Here, we construct a new transmission function by using as the probability density function a negative binomial distribution, and we develop a compartmental model using it to model the heterogeneity of contact rates in the population. We explore the transmission dynamics of the developed model using numerical simulations with different parameter settings, which characterize different levels of heterogeneity. The results show that when the reproductive number, R0, is larger than one, a low level of heterogeneity results in dynamics similar to those predicted by the homogeneous mixing model. As the level of heterogeneity increases, the dynamics become more different. As a test case, we calibrated the model with the case incidence data for severe acute respiratory syndrome (SARS) in Beijing in 2003, and the estimated parameters demonstrated the effectiveness of the control measures taken during that period. PMID:26927140

  9. Immunometabolism of obesity and diabetes: microbiota link compartmentalized immunity in the gut to metabolic tissue inflammation.

    PubMed

    McPhee, Joseph B; Schertzer, Jonathan D

    2015-12-01

    The bacteria that inhabit us have emerged as factors linking immunity and metabolism. Changes in our microbiota can modify obesity and the immune underpinnings of metabolic diseases such as Type 2 diabetes. Obesity coincides with a low-level systemic inflammation, which also manifests within metabolic tissues such as adipose tissue and liver. This metabolic inflammation can promote insulin resistance and dysglycaemia. However, the obesity and metabolic disease-related immune responses that are compartmentalized in the intestinal environment do not necessarily parallel the inflammatory status of metabolic tissues that control blood glucose. In fact, a permissive immune environment in the gut can exacerbate metabolic tissue inflammation. Unravelling these discordant immune responses in different parts of the body and establishing a connection between nutrients, immunity and the microbiota in the gut is a complex challenge. Recent evidence positions the relationship between host gut barrier function, intestinal T cell responses and specific microbes at the crossroads of obesity and inflammation in metabolic disease. A key problem to be addressed is understanding how metabolite, immune or bacterial signals from the gut are relayed and transferred into systemic or metabolic tissue inflammation that can impair insulin action preceding Type 2 diabetes. PMID:26464517

  10. Hypothalamic metabolic compartmentation during appetite regulation as revealed by magnetic resonance imaging and spectroscopy methods

    PubMed Central

    Lizarbe, Blanca; Benitez, Ania; Peláez Brioso, Gerardo A.; Sánchez-Montañés, Manuel; López-Larrubia, Pilar; Ballesteros, Paloma; Cerdán, Sebastián

    2013-01-01

    We review the role of neuroglial compartmentation and transcellular neurotransmitter cycling during hypothalamic appetite regulation as detected by Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) methods. We address first the neurochemical basis of neuroendocrine regulation in the hypothalamus and the orexigenic and anorexigenic feed-back loops that control appetite. Then we examine the main MRI and MRS strategies that have been used to investigate appetite regulation. Manganese-enhanced magnetic resonance imaging (MEMRI), Blood oxygenation level-dependent contrast (BOLD), and Diffusion-weighted magnetic resonance imaging (DWI) have revealed Mn2+ accumulations, augmented oxygen consumptions, and astrocytic swelling in the hypothalamus under fasting conditions, respectively. High field 1H magnetic resonance in vivo, showed increased hypothalamic myo-inositol concentrations as compared to other cerebral structures. 1H and 13C high resolution magic angle spinning (HRMAS) revealed increased neuroglial oxidative and glycolytic metabolism, as well as increased hypothalamic glutamatergic and GABAergic neurotransmissions under orexigenic stimulation. We propose here an integrative interpretation of all these findings suggesting that the neuroendocrine regulation of appetite is supported by important ionic and metabolic transcellular fluxes which begin at the tripartite orexigenic clefts and become extended spatially in the hypothalamus through astrocytic networks becoming eventually MRI and MRS detectable. PMID:23781199

  11. Redesign of extensive protein–DNA interfaces of meganucleases using iterative cycles of in vitro compartmentalization

    PubMed Central

    Takeuchi, Ryo; Choi, Michael; Stoddard, Barry L.

    2014-01-01

    LAGLIDADG homing endonucleases (meganucleases) are sequence-specific DNA cleavage enzymes used for genome engineering. Recently, meganucleases fused to transcription activator-like effectors have been demonstrated to efficiently introduce targeted genome modifications. However, retargeting meganucleases to genomic sequences of interest remains challenging because it usually requires extensive alteration of a large number of amino acid residues that are situated in and near the DNA interface. Here we describe an effective strategy to extensively redesign such an extensive biomolecular interface. Well-characterized meganucleases are computationally screened to identify the best candidate enzyme to target a genomic region; that protein is then redesigned using iterative rounds of in vitro selections within compartmentalized aqueous droplets, which enable screening of extremely large numbers of protein variants at each step. The utility of this approach is illustrated by engineering three different meganucleases to cleave three human genomic sites (found in two exons and one flanking intron in two clinically relevant genes) and a fourth endonuclease that discriminates between single-nucleotide polymorphism variants of one of those targets. Fusion with transcription activator-like effector DNA binding domains significantly enhances targeted modification induced by meganucleases engineered in this study. Simultaneous expression of two such fusion endonucleases results in efficient excision of a defined genomic region. PMID:24591643

  12. Compartmental modelling of the pharmacokinetics of a breast cancer resistance protein.

    PubMed

    Grandjean, Thomas R B; Chappell, Mike J; Yates, James T W; Jones, Kevin; Wood, Gemma; Coleman, Tanya

    2011-11-01

    A mathematical model for the pharmacokinetics of Hoechst 33342 following administration into a culture medium containing a population of transfected cells (HEK293 hBCRP) with a potent breast cancer resistance protein inhibitor, Fumitremorgin C (FTC), present is described. FTC is reported to almost completely annul resistance mediated by BCRP in vitro. This non-linear compartmental model has seven macroscopic sub-units, with 14 rate parameters. It describes the relationship between the concentration of Hoechst 33342 and FTC, initially spiked in the medium, and the observed change in fluorescence due to Hoechst 33342 binding to DNA. Structural identifiability analysis has been performed using two methods, one based on the similarity transformation/exhaustive modelling approach and the other based on the differential algebra approach. The analyses demonstrated that all models derived are uniquely identifiable for the experiments/observations available. A kinetic modelling software package, namely FACSIMILE (MPCA Software, UK), was used for parameter fitting and to obtain numerical solutions for the system equations. Model fits gave very good agreement with in vitro data provided by AstraZeneca across a variety of experimental scenarios. PMID:20971524

  13. Photoacoustic “nanobombs” fight against undesirable vesicular compartmentalization of anticancer drugs

    PubMed Central

    Chen, Aiping; Xu, Chun; Li, Min; Zhang, Hailin; Wang, Diancheng; Xia, Mao; Meng, Gang; Kang, Bin; Chen, Hongyuan; Wei, Jiwu

    2015-01-01

    Undesirable intracellular vesicular compartmentalization of anticancer drugs in cancer cells is a common cause of chemoresistance. Strategies aimed at circumventing this problem may improve chemotherapeutic efficacy. We report a novel photophysical strategy for controlled-disruption of vesicular sequestration of the anticancer drug doxorubicin (DOX). Single-walled carbon nanotubes (SWCNTs), modified with folate, were trapped in acidic vesicles after entering lung cancer cells. Upon irradiation by near-infrared pulsed laser, these vesicles were massively broken by the resulting photoacoustic shockwave, and the vesicle-sequestered contents were released, leading to redistribution of DOX from cytoplasm to the target-containing nucleus. Redistribution resulted in 12-fold decrease of the EC50 of DOX in lung cancer cells, and enhanced antitumor efficacy of low-dose DOX in tumor-bearing mice. Side effects were not observed. These findings provide insights of using nanotechnology to improve cancer chemotherapy, i.e. not only for drug delivery, but also for overcoming intracellular drug-transport hurdles. PMID:26483341

  14. Compartmentalization of metals within the diverse colloidal matrices comprising activated sludge microbial flocs.

    PubMed

    Leppard, Gary G; Droppo, Ian G; West, M Marcia; Liss, Steven N

    2003-01-01

    Activated sludge floc from a wastewater treatment system was characterized, with regard to principal structural, chemical, and microbiological components and properties, in relation to contaminant-colloid associations and settling. Multiscale analytical microscopies, in conjunction with multimethod sample preparations, were used correlatively to characterize diverse colloidal matrices within microbial floc. Transmission electron microscopy, in conjunction with energy dispersive spectroscopy (EDS), revealed specific associations of contaminant heavy metals with individual bacterial cells and with extracellular polymeric substances (EPS). Floc structure was mapped from the level of gross morphology down to the nano-scale, and flocs were described with respect to settling properties, size, shape, density, porosity, bound water content, and EPS chemical composition; gross surface properties were also measured for correlation with principal floc features. Compartmentalization results based on 171 EDS analyses and representative high-resolution images showed that nano-scale agglomerations of (i) silver (100%) and (ii) zinc (91%) were confined almost entirely to EPS matrices while (iii) Pb (100%) was confined to intracellular granules and (iv) aluminum was partitioned between EPS matrices (41%) and intracellular matrices (59%). The results suggest that engineered changes in microbial physiology and/or in macromolecular EPS composition may influence metal removal efficiencies. PMID:14674532

  15. A bulk sub-femtoliter in vitro compartmentalization system using super-fine electrosprays

    PubMed Central

    Sharma, Bineet; Takamura, Yuzuru; Shimoda, Tatsuya; Biyani, Manish

    2016-01-01

    The extreme miniaturization of biological and chemical assays in aqueous-droplet compartments enables spatiotemporal control for large-scale parallel experimentation and can thus permit new capabilities for “digitizing” directed molecular evolution methodologies. We report a remarkably facile bulk method to generate mega-scale monodisperse sub-femtoliter aqueous droplets by electrospray, using a prototype head with super-fine inkjet technology. Moreover, the electrostatic inkjet nozzle that injects the aqueous phase when immersed within an immiscible phase (an optimized oil/surfactant mixture) has the advantage of generating cell-like sub-femtoliter compartments for biomolecule encapsulation and successive biological and chemical reactions. Sub-femtoliter droplets of both liquid (water-in-oil, volumes ranging from 0.2 to 6.4 fL) and gel bead (agarose-in-oil, volume ranging from 0.3 to 15.6 fL) compartments with average sizes of 1.3 μm and 1.5 μm, respectively, were successfully generated using an inkjet nozzle at a speed of more than 105 droplets per second. We demonstrated the applicability of this system by synthesizing fluorescent proteins using a cell-free expression system inside electrosprayed sub-femtoliter droplets at an accelerated rate, thereby extending the utility of in vitro compartmentalization with improved analytical performance for a top-down artificial cellular system. PMID:27199080

  16. Technology Solutions Case Study: Apartment Compartmentalization with an Aerosol-Based Sealing Process

    SciTech Connect

    2015-07-01

    Air sealing of building enclosures is a difficult and time-consuming process. Current methods in new construction require laborers to physically locate small and sometimes large holes in multiple assemblies and then manually seal each of them. This research study by Building America team Consortium for Advanced Residential Buildings demonstrated the automated air sealing and compartmentalization of buildings through the use of an aerosolized sealant developed by the Western Cooling Efficiency Center at University of California Davis. CARB demonstrated this new technology application in a multifamily building in Queens, NY. The effectiveness of the sealing process was evaluated by three methods: air leakage testing of overall apartment before and after sealing, point-source testing of individual leaks, and pressure measurements in the walls of the target apartment during sealing. Aerosolized sealing was successful by several measures in this study. Many individual leaks that are labor-intensive to address separately were well sealed by the aerosol particles. In addition, many diffuse leaks that are difficult to identify and treat were also sealed. The aerosol-based sealing process resulted in an average reduction of 71% in air leakage across three apartments and an average apartment airtightness of 0.08 CFM50/SF of enclosure area.

  17. Compartmentalization of the exocyst complex in lipid rafts controls Glut4 vesicle tethering.

    PubMed

    Inoue, Mayumi; Chiang, Shian-Huey; Chang, Louise; Chen, Xiao-Wei; Saltiel, Alan R

    2006-05-01

    Lipid raft microdomains act as organizing centers for signal transduction. We report here that the exocyst complex, consisting of Exo70, Sec6, and Sec8, regulates the compartmentalization of Glut4-containing vesicles at lipid raft domains in adipocytes. Exo70 is recruited by the G protein TC10 after activation by insulin and brings with it Sec6 and Sec8. Knockdowns of these proteins block insulin-stimulated glucose uptake. Moreover, their targeting to lipid rafts is required for glucose uptake and Glut4 docking at the plasma membrane. The assembly of this complex also requires the PDZ domain protein SAP97, a member of the MAGUKs family, which binds to Sec8 upon its translocation to the lipid raft. Exocyst assembly at lipid rafts sets up targeting sites for Glut4 vesicles, which transiently associate with these microdomains upon stimulation of cells with insulin. These results suggest that the TC10/exocyst complex/SAP97 axis plays an important role in the tethering of Glut4 vesicles to the plasma membrane in adipocytes. PMID:16525015

  18. Modeling the time dependent biodistribution of Samarium-153 ethylenediamine tetramethylene phosphonate using compartmental analysis

    PubMed Central

    Abbasian, Parandoush; Foroghy, Monika; Jalilian, Amir Reza; Hakimi, Amir; Shirvani-Arani, Simindokht

    2013-01-01

    Aim The main purpose of this work was to develop a pharmacokinetic model for the bone pain palliation agent Samarium-153 ethylenediamine tetramethylene phosphonate ([153Sm]-EDTMP) in normal rats to analyze the behavior of the complex. Background The use of compartmental analysis allows a mathematical separation of tissues and organs to determine the concentration of activity in each fraction of interest. Biodistribution studies are expensive and difficult to carry out in humans, but such data can be obtained easily in rodents. Materials and methods We have developed a physiologically based pharmacokinetic model for scaling up activity concentration in each organ versus time. The mathematical model uses physiological parameters including organ volumes, blood flow rates, and vascular permabilities; the compartments (organs) are connected anatomically. This allows the use of scale-up techniques to predict new complex distribution in humans in each organ. Results The concentration of the radiopharmaceutical in various organs was measured at different times. The temporal behavior of biodistribution of 153Sm-EDTMP was modeled and drawn as a function of time. Conclusions The variation of pharmaceutical concentration in all organs is described with summation of 6–10 exponential terms and it approximates our experimental data with precision better than 2%. PMID:24936338

  19. Plasma Membrane Polarity and Compartmentalization are Established Before Cellularization in the Fly Embryo

    PubMed Central

    Mavrakis, Manos; Rikhy, Richa; Lippincott-Schwartz, Jennifer

    2009-01-01

    Summary Patterning in the Drosophila embryo requires local activation and dynamics of proteins in the plasma membrane (PM). We used in vivo fluorescence imaging to characterize the organization and diffusional properties of the PM in the early embryonic syncytium. Before cellularization, the PM is polarized into discrete domains having epithelial-like characteristics. One domain resides above individual nuclei and has apical-like characteristics, while the other domain is lateral to nuclei and contains markers associated with basolateral membranes and junctions. Pulse-chase photoconversion experiments show that molecules can diffuse within each domain but do not exchange between PM regions above adjacent nuclei. Drug-induced F-actin depolymerization disrupted both the apicobasal-like polarity and the diffusion barriers within the syncytial PM. These events correlated with perturbations in the spatial pattern of dorsoventral Toll signaling. We propose that epithelial-like properties and an intact F-actin network compartmentalize the PM and shape morphogen gradients in the syncytial embryo. PMID:19154721

  20. Sub-Compartmental Organization of Golgi-Resident N-Glycan Processing Enzymes in Plants

    PubMed Central

    Schoberer, Jennifer; Strasser, Richard

    2011-01-01

    In all eukaryotes, the Golgi apparatus is the main site of protein glycosylation. It is widely accepted that the glycosidases and glycosyltransferases involved in N-glycan processing are found concentrated within the Golgi stack where they provide their function. This means that enzymes catalyzing early steps in the processing pathway are located mainly at the cis-side, whereas late-acting enzymes mostly locate to the trans-side of the stacks, creating a non-uniform distribution along the cis–trans axis of the Golgi. There is compelling evidence that the information for their sorting to specific Golgi cisternae depends on signals encoded in the proteins themselves as well as on the trafficking machinery that recognizes these signals and it is believed that cisternal sub-compartmentalization is achieved and maintained by a combination of retention and retrieval mechanisms. Yet, the signals, mechanism(s), and molecular factors involved are still unknown. Here, we address recent findings and summarize the current understanding of this fundamental process in plant cell biology. PMID:21307368

  1. Compartmental microfluidic system for studying muscle-neuron communication and neuromuscular junction maintenance.

    PubMed

    Ionescu, Ariel; Zahavi, Eitan Erez; Gradus, Tal; Ben-Yaakov, Keren; Perlson, Eran

    2016-02-01

    Molecular communication between the motoneuron and the muscle is vital for neuromuscular junction (NMJ) formation and maintenance. Disruption in the structure and function of NMJs is a hallmark of various neurodegenerative processes during both development and pathological events. Still due to the complexity of this process, it is very difficult to elucidate the cellular mechanisms underlying it, generating a keen interest for developing better tools for investigating it. Here we describe a simplified method to study mechanisms of NMJs formation, maintenance and disruption. A spinal cord explant from mice expressing the Hb9::GFP motoneuron marker is plated on one side of a compartmental chamber, and myotubes derived from muscle satellite progenitor cells are plated on the other. The GFP labeled motoneurons extend their axons via microgrooves in the chamber to innervate the muscle cells and to form functional in-vitro NMJs. Next we provide procedures to measure axon growth and to reliably quantify NMJ activity using imaging of both muscle contractions and fast intracellular calcium changes. This platform allows precise control, monitoring and manipulation of subcellular microenvironments. Specifically, it enables to distinguish local from retrograde signaling mechanisms and allows restricted experimental intervention in local compartments along the muscle-neuron route. PMID:26689471

  2. A Tale of Genome Compartmentalization: The Evolution of Virulence Clusters in Smut Fungi

    PubMed Central

    Dutheil, Julien Y.; Mannhaupt, Gertrud; Schweizer, Gabriel; M.K. Sieber, Christian; Münsterkötter, Martin; Güldener, Ulrich; Schirawski, Jan; Kahmann, Regine

    2016-01-01

    Smut fungi are plant pathogens mostly parasitizing wild species of grasses as well as domesticated cereal crops. Genome analysis of several smut fungi including Ustilago maydis revealed a singular clustered organization of genes encoding secreted effectors. In U. maydis, many of these clusters have a role in virulence. Reconstructing the evolutionary history of clusters of effector genes is difficult because of their intrinsically fast evolution, which erodes the phylogenetic signal and homology relationships. Here, we describe the use of comparative evolutionary analyses of quality draft assemblies of genomes to study the mechanisms of this evolution. We report the genome sequence of a South African isolate of Sporisorium scitamineum, a smut fungus parasitizing sugar cane with a phylogenetic position intermediate to the two previously sequenced species U. maydis and Sporisorium reilianum. We show that the genome of S. scitamineum contains more and larger gene clusters encoding secreted effectors than any previously described species in this group. We trace back the origin of the clusters and find that their evolution is mainly driven by tandem gene duplication. In addition, transposable elements play a major role in the evolution of the clustered genes. Transposable elements are significantly associated with clusters of genes encoding fast evolving secreted effectors. This suggests that such clusters represent a case of genome compartmentalization that restrains the activity of transposable elements on genes under diversifying selection for which this activity is potentially beneficial, while protecting the rest of the genome from its deleterious effect. PMID:26872771

  3. Compartmentation and turnover of the low density lipoprotein receptor in skin fibroblasts.

    PubMed

    Hare, J F

    1990-12-15

    The low density lipoprotein receptor (LDLR) was immunoprecipitated from [35S]methionine-labeled skin fibroblasts derivatized at 4 or 18 degrees C with an impermeant biotinylating reagent. Separation of derivatized and underivatized receptor from immunoprecipitates by selective binding to streptavidin-agarose allowed assessment of receptor protein cellular compartmentation and rates of intercompartmental transfer. At both 4 and 18 degrees C the amount of LDLR that is derivatized in cells labeled to near steady state saturates after 1-2 h of reaction at, respectively, 47 and 70% of total immunoprecipitable receptor protein. On the basis of temperature titration experiments, protein exposed only to the cell surface reacts at 4 degrees C; raising the temperature of biotinylation to 18 degrees C provides access to an additional pool of receptor protein. Remaining LDLR is derivatized at 37 degrees C. LDLR unreactive at 18 degrees C largely resides in membrane compartment(s) devoid of plasma membrane on the basis of its fractionation on Percoll gradients. While total cellular LDLR and 4 degrees C-derivatized LDLR labeled to steady state turn over in a first order manner (t1/2 = 12-13 h), the specific activity of pulse-labeled, 4 degrees C-accessible protein peaks after 1-2 h of chase and reaches a reduced level by 3 h of chase. These latter results show that the newly synthesized LDLR is transiently enriched at the cell surface prior to achieving equilibrium distribution between the cell surface and intracellular pools. PMID:2254328

  4. Compartmentalized Epidermal Activation of β-Catenin Differentially Affects Lineage Reprogramming and Underlies Tumor Heterogeneity

    PubMed Central

    Kretzschmar, Kai; Weber, Christine; Driskell, Ryan R.; Calonje, Eduardo; Watt, Fiona M.

    2016-01-01

    Summary Wnt/β-catenin activation in adult epidermis can induce new hair follicle formation and tumor development. We used lineage tracing to uncover the relative contribution of different stem cell populations. LGR6+ and LRIG1+ stem cells contributed to ectopic hair follicles formed in the sebaceous gland upon β-catenin activation, whereas LGR5+ cells did not. Lgr6, but not Lrig1 or Lgr5, was expressed in a subpopulation of interfollicular epidermal cells that were competent to form new hair follicles. Oncogenic β-catenin expression in LGR5+ cells led to formation of pilomatricomas, while LRIG1+ cells formed trichoadenomas and LGR6+ cells formed dermatofibromas. Tumor formation was always accompanied by a local increase in dermal fibroblast density and transient extracellular matrix remodeling. However, each tumor had a distinct stromal signature in terms of immune cell infiltrate and expression of CD26 and CD44. We conclude that compartmentalization of epidermal stem cells underlies different responses to β-catenin and skin tumor heterogeneity. PMID:26771241

  5. Predicting abundances of plants and pollinators using a simple compartmental mutualistic model.

    PubMed

    Fort, Hugo; Mungan, Muhittin

    2015-06-01

    Key gaps to be filled in population and community ecology are predicting the strength of species interactions and linking pattern with process to understand species coexistence and their relative abundances. In the case of mutualistic webs, like plant-pollinator networks, advances in understanding species abundances are currently limited, mainly owing to the lack of methodological tools to deal with the intrinsic complexity of mutualisms. Here, we propose an aggregation method leading to a simple compartmental mutualistic population model that captures both qualitatively and quantitatively the size-segregated populations observed in a Mediterranean community of nectar-producing plant species and nectar-searching animal species. We analyse the issue of optimal aggregation level and its connection with the trade-off between realism and overparametrization. We show that aggregation of both plants and pollinators into five size classes or compartments leads to a robust model with only two tunable parameters. Moreover, if, in each compartment, (i) the interaction coefficients fulfil the condition of weak mutualism and (ii) the mutualism is facultative for at least one party of the compartment, then the interactions between different compartments are sufficient to guarantee global stability of the equilibrium population. PMID:25948690

  6. Quantitative Analysis of Axonal Transport by Using Compartmentalized and Surface Micropatterned Culture of Neurons

    PubMed Central

    2012-01-01

    Mitochondria, synaptic vesicles, and other cytoplasmic constituents have to travel long distance along the axons from cell bodies to nerve terminals. Interruption of this axonal transport may contribute to many neurodegenerative diseases including Alzheimer’s disease (AD). It has been recently shown that exposure of cultured neurons to β-amyloid (Aβ) resulted in severe impairment of mitochondrial transport. This Letter describes an integrated microfluidic platform that establishes surface patterned and compartmentalized culture of neurons for studying the effect of Aβ on mitochondria trafficking in full length of axons. We have successfully quantified the trafficking of fluorescently labeled mitochondria in distal and proximal axons using image processing. Selective treatment of Aβ in the somal or axonal compartments resulted in considerable decrease in mitochondria movement in a location dependent manner such that mitochondria trafficking slowed down more significantly proximal to the location of Aβ exposure. Furthermore, this result suggests a promising application of microfluidic technology for investigating the dysfunction of axonal transport related to neurodegenerative diseases. PMID:24358503

  7. Modeling Heterogeneity in Direct Infectious Disease Transmission in a Compartmental Model.

    PubMed

    Kong, Lingcai; Wang, Jinfeng; Han, Weiguo; Cao, Zhidong

    2016-03-01

    Mathematical models have been used to understand the transmission dynamics of infectious diseases and to assess the impact of intervention strategies. Traditional mathematical models usually assume a homogeneous mixing in the population, which is rarely the case in reality. Here, we construct a new transmission function by using as the probability density function a negative binomial distribution, and we develop a compartmental model using it to model the heterogeneity of contact rates in the population. We explore the transmission dynamics of the developed model using numerical simulations with different parameter settings, which characterize different levels of heterogeneity. The results show that when the reproductive number, R₀, is larger than one, a low level of heterogeneity results in dynamics similar to those predicted by the homogeneous mixing model. As the level of heterogeneity increases, the dynamics become more different. As a test case, we calibrated the model with the case incidence data for severe acute respiratory syndrome (SARS) in Beijing in 2003, and the estimated parameters demonstrated the effectiveness of the control measures taken during that period. PMID:26927140

  8. A Tale of Genome Compartmentalization: The Evolution of Virulence Clusters in Smut Fungi.

    PubMed

    Dutheil, Julien Y; Mannhaupt, Gertrud; Schweizer, Gabriel; M K Sieber, Christian; Münsterkötter, Martin; Güldener, Ulrich; Schirawski, Jan; Kahmann, Regine

    2016-03-01

    Smut fungi are plant pathogens mostly parasitizing wild species of grasses as well as domesticated cereal crops. Genome analysis of several smut fungi including Ustilago maydis revealed a singular clustered organization of genes encoding secreted effectors. In U. maydis, many of these clusters have a role in virulence. Reconstructing the evolutionary history of clusters of effector genes is difficult because of their intrinsically fast evolution, which erodes the phylogenetic signal and homology relationships. Here, we describe the use of comparative evolutionary analyses of quality draft assemblies of genomes to study the mechanisms of this evolution. We report the genome sequence of a South African isolate of Sporisorium scitamineum, a smut fungus parasitizing sugar cane with a phylogenetic position intermediate to the two previously sequenced species U. maydis and Sporisorium reilianum. We show that the genome of S. scitamineum contains more and larger gene clusters encoding secreted effectors than any previously described species in this group. We trace back the origin of the clusters and find that their evolution is mainly driven by tandem gene duplication. In addition, transposable elements play a major role in the evolution of the clustered genes. Transposable elements are significantly associated with clusters of genes encoding fast evolving secreted effectors. This suggests that such clusters represent a case of genome compartmentalization that restrains the activity of transposable elements on genes under diversifying selection for which this activity is potentially beneficial, while protecting the rest of the genome from its deleterious effect. PMID:26872771

  9. Intracellular compartmentation of isozymes of sugar phosphate metabolism in green leaves.

    PubMed

    Schnarrenberger, C; Herbert, M; Krüger, I

    1983-01-01

    The present paper has summarized evidence for the presence of two isozymes for many enzyme activities of sugar phosphate metabolism in plant leaves. These two isozymes are clearly compartmentalized in the chloroplasts and in the cytosol of plant leaf cells. In C4 plants there exists an additional isozyme in the mesophyll cells of these leaves in addition to the two isozymes in the bundle sheath cells. Such cell-compartment-specific and cell-specific isozymes provide duplicate (and possibly triplicate) enzyme systems for complete or almost complete pathways (ie, glycolysis, gluconeogenesis, and the oxidative pentose phosphate pathway). They provide a basis for the understanding as to how many isozymes one may expect in plants. They also provide a challenge to determine what their function is particularly in the differential regulation of metabolic pathways in different cell compartments. Based on his genetic analyses Weeden [1981] has recently proposed a model for the evolution of chloroplast-specific isozymes of sugar phosphate metabolism. This model rests on the endosymbiotic theory for the origin of chloroplasts. It still is highly speculative. However, cell-compartment specific isozymes may eventually provide a means of studying plant evolution, especially if we succeed in analyzing their primary structure. PMID:6629713

  10. Origin and evolution of metabolic sub-cellular compartmentalization in eukaryotes

    PubMed Central

    Gabaldón, Toni; Pittis, Alexandros A.

    2015-01-01

    A high level of subcellular compartmentalization is a hallmark of eukaryotic cells. This intricate internal organization was present already in the common ancestor of all extant eukaryotes, and the determination of the origins and early evolution of the different organelles remains largely elusive. Organellar proteomes are determined through regulated pathways that target proteins produced in the cytosol to their final subcellular destinations. This internal sorting of proteins can vary across different physiological conditions, cell types and lineages. Evolutionary retargeting – the alteration of a subcellular localization of a protein in the course of evolution – has been rampant in eukaryotes and involves any possible combination of organelles. This fact adds another layer of difficulty to the reconstruction of the origins and evolution of organelles. In this review we discuss current themes in relation to the origin and evolution of organellar proteomes. Throughout the text, a special focus is set on the evolution of mitochondrial and peroxisomal proteomes, which are two organelles for which extensive proteomic and evolutionary studies have been performed. PMID:25869000

  11. Local Microenvironment Controls the Compartmentalization of NK Cell Responses during Systemic Inflammation in Mice.

    PubMed

    Rasid, Orhan; Ciulean, Ioana Sonya; Fitting, Catherine; Doyen, Noelle; Cavaillon, Jean-Marc

    2016-09-15

    Systemic inflammatory response syndrome is a whole-body reaction to a triggering insult that often results in life-threatening illness. Contributing to the development of this inflammatory cascade are numerous cellular partners, among which NK cells were shown to play a key role. Accumulating evidence points to organ-specific properties of systemic inflammation and NK cells. However, little is known about compartment-specific activation of NK cells during systemic inflammatory response syndrome or the relative contribution of NK cell-intrinsic properties and microenvironmental cues. In this study, we undertook a sequential characterization of NK responses in the spleen, lungs, bone marrow, peritoneum, and blood using a mouse model of endotoxemia. We report that, despite similar systemic dynamics of NK cell responses, expression of activation markers (CD69 and CD25) and effector molecules (IFN-γ, granzyme B, and IL-10) display organ-specific thresholds of maximum activation. Using adoptive transfers of spleen and lung NK cells, we found that these cells have the capacity to quickly adapt to a new environment and adjust their response levels to that of resident NK cells. This functional adaptation occurs without significant alterations in phenotype and independently of subpopulation-specific trafficking. Thus, using a dynamic in vivo-transfer system, to our knowledge our study is the first to report the compartmentalization of NK cells responses during systemic inflammation and to show that NK cell-intrinsic properties and microenvironmental cues are involved in this process, in a sequential manner. PMID:27521338

  12. Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units.

    PubMed

    Uzel, Sebastien G M; Platt, Randall J; Subramanian, Vidya; Pearl, Taylor M; Rowlands, Christopher J; Chan, Vincent; Boyer, Laurie A; So, Peter T C; Kamm, Roger D

    2016-08-01

    Motor units are the fundamental elements responsible for muscle movement. They are formed by lower motor neurons and their muscle targets, synapsed via neuromuscular junctions (NMJs). The loss of NMJs in neurodegenerative disorders (such as amyotrophic lateral sclerosis or spinal muscle atrophy) or as a result of traumatic injuries affects millions of lives each year. Developing in vitro assays that closely recapitulate the physiology of neuromuscular tissues is crucial to understand the formation and maturation of NMJs, as well as to help unravel the mechanisms leading to their degeneration and repair. We present a microfluidic platform designed to coculture myoblast-derived muscle strips and motor neurons differentiated from mouse embryonic stem cells (ESCs) within a three-dimensional (3D) hydrogel. The device geometry mimics the spinal cord-limb physical separation by compartmentalizing the two cell types, which also facilitates the observation of 3D neurite outgrowth and remote muscle innervation. Moreover, the use of compliant pillars as anchors for muscle strips provides a quantitative functional readout of force generation. Finally, photosensitizing the ESC provides a pool of source cells that can be differentiated into optically excitable motor neurons, allowing for spatiodynamic, versatile, and noninvasive in vitro control of the motor units. PMID:27493991

  13. Dissecting the Subcellular Compartmentation of Proteins and Metabolites in Arabidopsis Leaves Using Non-aqueous Fractionation *

    PubMed Central

    Arrivault, Stéphanie; Guenther, Manuela; Florian, Alexandra; Encke, Beatrice; Feil, Regina; Vosloh, Daniel; Lunn, John E.; Sulpice, Ronan; Fernie, Alisdair R.; Stitt, Mark; Schulze, Waltraud X.

    2014-01-01

    Non-aqueous fractionation is a technique for the enrichment of different subcellular compartments derived from lyophilized material. It was developed to study the subcellular distribution of metabolites. Here we analyzed the distribution of about 1,000 proteins and 70 metabolites, including 22 phosphorylated intermediates in wild-type Arabidopsis rosette leaves, using non-aqueous gradients divided into 12 fractions. Good separation of plastidial, cytosolic, and vacuolar metabolites and proteins was achieved, but cytosolic, mitochondrial, and peroxisomal proteins clustered together. There was considerable heterogeneity in the fractional distribution of transcription factors, ribosomal proteins, and subunits of the vacuolar-ATPase, indicating diverse compartmental location. Within the plastid, sub-organellar separation of thylakoids and stromal proteins was observed. Metabolites from the Calvin–Benson cycle, photorespiration, starch and sucrose synthesis, glycolysis, and the tricarboxylic acid cycle grouped with their associated proteins of the respective compartment. Non-aqueous fractionation thus proved to be a powerful method for the study of the organellar, and in some cases sub-organellar, distribution of proteins and their association with metabolites. It remains the technique of choice for the assignment of subcellular location to metabolites in intact plant tissues, and thus the technique of choice for doing combined metabolite–protein analysis on a single tissue sample. PMID:24866124

  14. Compartmentalized Acyl-CoA Metabolism in Skeletal Muscle Regulates Systemic Glucose Homeostasis

    PubMed Central

    Li, Lei O.; Grevengoed, Trisha J.; Paul, David S.; Ilkayeva, Olga; Koves, Timothy R.; Pascual, Florencia; Newgard, Christopher B.; Muoio, Deborah M.

    2015-01-01

    The impaired capacity of skeletal muscle to switch between the oxidation of fatty acid (FA) and glucose is linked to disordered metabolic homeostasis. To understand how muscle FA oxidation affects systemic glucose, we studied mice with a skeletal muscle–specific deficiency of long-chain acyl-CoA synthetase (ACSL)1. ACSL1 deficiency caused a 91% loss of ACSL-specific activity and a 60–85% decrease in muscle FA oxidation. Acsl1M−/− mice were more insulin sensitive, and, during an overnight fast, their respiratory exchange ratio was higher, indicating greater glucose use. During endurance exercise, Acsl1M−/− mice ran only 48% as far as controls. At the time that Acsl1M−/− mice were exhausted but control mice continued to run, liver and muscle glycogen and triacylglycerol stores were similar in both genotypes; however, plasma glucose concentrations in Acsl1M−/− mice were ∼40 mg/dL, whereas glucose concentrations in controls were ∼90 mg/dL. Excess use of glucose and the likely use of amino acids for fuel within muscle depleted glucose reserves and diminished substrate availability for hepatic gluconeogenesis. Surprisingly, the content of muscle acyl-CoA at exhaustion was markedly elevated, indicating that acyl-CoAs synthesized by other ACSL isoforms were not available for β-oxidation. This compartmentalization of acyl-CoAs resulted in both an excessive glucose requirement and severely compromised systemic glucose homeostasis. PMID:25071025

  15. A clickable neurosteroid photolabel reveals selective Golgi compartmentalization with preferential impact on proximal inhibition.

    PubMed

    Jiang, Xiaoping; Shu, Hong-Jin; Krishnan, Kathiresan; Qian, Mingxing; Taylor, Amanda A; Covey, Douglas F; Zorumski, Charles F; Mennerick, Steven

    2016-09-01

    Anesthetic, GABA-active neurosteroids potently augment GABAA receptor function, leading to important behavioral consequences. Neurosteroids and their synthetic analogues are also models for a wide variety of cell-permeant neuroactive compounds. Cell permeation and compartmentalization raise the possibility that these compounds' actions are influenced by their cellular partitioning, but these contributions are not typically considered experimentally or therapeutically. To examine the interplay between cellular accumulation and pharmacodynamics of neurosteroids, we synthesized a novel chemical biology analogue (bio-active, clickable photolabel) of GABA-active neurosteroids. We discovered that the analogue selectively photo-labels neuronal Golgi in rat hippocampal neurons. The active analogue's selective distribution was distinct from endogenous cholesterol and not completely shared by some non-GABA active, neurosteroid-like analogues. On the other hand, the distribution was not enantioselective and did not require energy, in contrast to other recent precedents from the literature. We demonstrate that the soma-selective accumulation can act as a sink or source for steroid actions at plasma-membrane GABA receptors, altering steady-state and time course of effects at somatic GABAA receptors relative to dendritic receptors. Our results suggest a novel mechanism for compartment-selective drug actions at plasma-membrane receptors. PMID:27114255

  16. A nanoliter self-priming compartmentalization chip for point-of-care digital PCR analysis.

    PubMed

    Song, Qi; Gao, Yibo; Zhu, Qiangyuan; Tian, Qingchang; Yu, Bingwen; Song, Bofan; Xu, Yanan; Yuan, Maokai; Ma, Congcong; Jin, Wei; Zhang, Tao; Mu, Ying; Jin, Qinhan

    2015-01-01

    A nanoliter self-priming compartmentalization (SPC) microfluidic chip suited for the digital polymerase chain reaction (dPCR) analysis in point-of-care testing (POCT) has been developed. This dPCR chip is fabricated of polydimethylsiloxane (PDMS). After the dPCR chip is evacuated, there will be a negative pressure environment in the chip because of the gas solubility of PDMS. The negative pressure environment can provide a self-priming power so that the sample solutions can be sucked into each reaction chamber sequentially. The whole sampling process requires no external power and is valve-free. Channels that contain water are designed around each sample panel to prevent the solvent (water) from evaporating during dPCR process. A glass coverslip is also used as a waterproof layer, which is more convenient and more efficient than other waterproof methods seen in literature. This dPCR chip allows three samples to be amplified at the same time. Each sample is distributed into 1040 reaction chambers, and each chamber is only 2.08 nL. Human β-actin DNA solutions of known concentrations are used as the templates for the dPCR analyses to verify the sensitivity and accuracy of the method. Template DNA solutions diluted to concentrations of 300, 100 and 10 copies/μL are tested and shown that this simple, portable and self-priming dPCR chip can be used at any clinic as a real POCT technique. PMID:26022215

  17. A nanoliter self-priming compartmentalization chip for point-of-care digital PCR analysis.

    PubMed

    Song, Qi; Gao, Yibo; Zhu, Qiangyuan; Tian, Qingchang; Yu, Bingwen; Song, Bofan; Xu, Yanan; Yuan, Maokai; Ma, Congcong; Jin, Wei; Zhang, Tao; Mu, Ying; Jin, Qinhan

    2015-01-01

    A nanoliter self-priming compartmentalization (SPC) microfluidic chip suited for the digital polymerase chain reaction (dPCR) analysis in point-of-care testing (POCT) has been developed. This dPCR chip is fabricated of polydimethylsiloxane (PDMS). After the dPCR chip is evacuated, there will be a negative pressure environment in the chip because of the gas solubility of PDMS. The negative pressure environment can provide a self-priming power so that the sample solutions can be sucked into each reaction chamber sequentially. The whole sampling process requires no external power and is valve-free. Channels that contain water are designed around each sample panel to prevent the solvent (water) from evaporating during dPCR process. A glass coverslip is also used as a waterproof layer, which is more convenient and more efficient than other waterproof methods seen in literature. This dPCR chip allows three samples to be amplified at the same time. Each sample is distributed into 1040 reaction chambers, and each chamber is only 2.08 nL. Human β-actin DNA solutions of known concentrations are used as the templates for the dPCR analyses to verify the sensitivity and accuracy of the method. Template DNA solutions diluted to concentrations of 300, 100 and 10 copies/μL are tested and shown that this simple, portable and self-priming dPCR chip can be used at any clinic as a real POCT technique. PMID:26029750

  18. Leishmania amazonensis Arginase Compartmentalization in the Glycosome Is Important for Parasite Infectivity

    PubMed Central

    da Silva, Maria Fernanda Laranjeira; Zampieri, Ricardo Andrade; Muxel, Sandra M.; Beverley, Stephen M.; Floeter-Winter, Lucile M.

    2012-01-01

    In Leishmania, de novo polyamine synthesis is initiated by the cleavage of L-arginine to urea and L-ornithine by the action of arginase (ARG, E.C. 3.5.3.1). Previous studies in L. major and L. mexicana showed that ARG is essential for in vitro growth in the absence of polyamines and needed for full infectivity in animal infections. The ARG protein is normally found within the parasite glycosome, and here we examined whether this localization is required for survival and infectivity. First, the localization of L. amazonensis ARG in the glycosome was confirmed in both the promastigote and amastigote stages. As in other species, arg− L. amazonensis required putrescine for growth and presented an attenuated infectivity. Restoration of a wild type ARG to the arg− mutant restored ARG expression, growth and infectivity. In contrast, restoration of a cytosol-targeted ARG lacking the glycosomal SKL targeting sequence (argΔSKL) restored growth but failed to restore infectivity. Further study showed that the ARGΔSKL protein was found in the cytosol as expected, but at very low levels. Our results indicate that the proper compartmentalization of L. amazonensis arginase in the glycosome is important for enzyme activity and optimal infectivity. Our conjecture is that parasite arginase participates in a complex equilibrium that defines the fate of L-arginine and that its proper subcellular location may be essential for this physiological orchestration. PMID:22479507

  19. Compartmentalization of cerebral cortical germinal zones in a lissencephalic primate and gyrencephalic rodent.

    PubMed

    García-Moreno, Fernando; Vasistha, Navneet A; Trevia, Nonata; Bourne, James A; Molnár, Zoltán

    2012-02-01

    Previous studies of macaque and human cortices identified cytoarchitectonically distinct germinal zones; the ventricular zone inner subventricular zone (ISVZ), and outer subventricular zone (OSVZ). To date, the OSVZ has only been described in gyrencephalic brains, separated from the ISVZ by an inner fiber layer and considered a milestone that triggered increased neocortical neurogenesis. However, this observation has only been assessed in a handful of species without the identification of the different progenitor populations. We examined the Amazonian rodent agouti (Dasyprocta agouti) and the marmoset monkey (Callithrix jacchus) to further understand relationships among progenitor compartmentalization, proportions of various cortical progenitors, and degree of cortical folding. We identified a similar cytoarchitectonic distinction between the OSVZ and ISVZ at midgestation in both species. In the marmoset, we quantified the ventricular and abventricular divisions and observed similar proportions as previously described for the human and ferret brains. The proportions of radial glia, intermediate progenitors, and outer radial glial cell (oRG) populations were similar in midgestation lissencephalic marmoset as in gyrencephalic human or ferret. Our findings suggest that cytoarchitectonic subdivisions of SVZ are an evolutionary trend and not a primate specific feature, and a large population of oRG can be seen regardless of cortical folding. PMID:22114081

  20. Fluvial architecture and reservoir compartmentalization in the Oligocene middle Frio Formation of south Texas

    SciTech Connect

    Kerr, D.R.; Jirik, L.A. )

    1990-09-01

    Seeligson, Stratton, and Agua Dulce fields are being studied as part of a Gas Research Institute/Department of Energy/State of Texas cosponsored program designed to develop and test methodologies and technologies for gas reserve growth in conventional reservoirs in mature gas fields. Over the last four decades, each field has produced approximately 2 tcf of gas from middle Frio reservoirs alone. Recent drilling and workover results and reservoir pressure data, however, point to the possibility of additional reserves. Stratigraphic and sedimentologic studies based on well logs and cores indicate that middle Frio reservoirs are architecturally complex. Deposition on an aggrading coastal plain resulted in a continuum of architectural styles that has important implications for reservoir compartmentalization. The middle Frio is composed of sand-rich channel-fill and splay deposits interstratified with floodplain mudstones, all forming part of the Gueydan fluvial system. Relatively slow aggradation resulted in laterally stacked channel systems; whereas more rapid aggradation resulted in vertically stacked channel systems. Laterally stacked sandstone bodies predominate at Seeligson field, leading to separate but potentially leaky reservoir compartments. By contrast, vertically stacked sandstone bodies predominate at Stratton and Agua Dulce fields, favoring more isolated reservoir compartments. Thus, a high potential for reserve growth through the identification of untapped compartments, poorly drained acreage, and bypassed zones exists for each of these fields, but differences in reservoir architecture must be taken into account as part of exploitation strategies.

  1. Predicting abundances of plants and pollinators using a simple compartmental mutualistic model

    PubMed Central

    Fort, Hugo; Mungan, Muhittin

    2015-01-01

    Key gaps to be filled in population and community ecology are predicting the strength of species interactions and linking pattern with process to understand species coexistence and their relative abundances. In the case of mutualistic webs, like plant–pollinator networks, advances in understanding species abundances are currently limited, mainly owing to the lack of methodological tools to deal with the intrinsic complexity of mutualisms. Here, we propose an aggregation method leading to a simple compartmental mutualistic population model that captures both qualitatively and quantitatively the size-segregated populations observed in a Mediterranean community of nectar-producing plant species and nectar-searching animal species. We analyse the issue of optimal aggregation level and its connection with the trade-off between realism and overparametrization. We show that aggregation of both plants and pollinators into five size classes or compartments leads to a robust model with only two tunable parameters. Moreover, if, in each compartment, (i) the interaction coefficients fulfil the condition of weak mutualism and (ii) the mutualism is facultative for at least one party of the compartment, then the interactions between different compartments are sufficient to guarantee global stability of the equilibrium population. PMID:25948690

  2. Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units

    PubMed Central

    Uzel, Sebastien G. M.; Platt, Randall J.; Subramanian, Vidya; Pearl, Taylor M.; Rowlands, Christopher J.; Chan, Vincent; Boyer, Laurie A.; So, Peter T. C.; Kamm, Roger D.

    2016-01-01

    Motor units are the fundamental elements responsible for muscle movement. They are formed by lower motor neurons and their muscle targets, synapsed via neuromuscular junctions (NMJs). The loss of NMJs in neurodegenerative disorders (such as amyotrophic lateral sclerosis or spinal muscle atrophy) or as a result of traumatic injuries affects millions of lives each year. Developing in vitro assays that closely recapitulate the physiology of neuromuscular tissues is crucial to understand the formation and maturation of NMJs, as well as to help unravel the mechanisms leading to their degeneration and repair. We present a microfluidic platform designed to coculture myoblast-derived muscle strips and motor neurons differentiated from mouse embryonic stem cells (ESCs) within a three-dimensional (3D) hydrogel. The device geometry mimics the spinal cord–limb physical separation by compartmentalizing the two cell types, which also facilitates the observation of 3D neurite outgrowth and remote muscle innervation. Moreover, the use of compliant pillars as anchors for muscle strips provides a quantitative functional readout of force generation. Finally, photosensitizing the ESC provides a pool of source cells that can be differentiated into optically excitable motor neurons, allowing for spatiodynamic, versatile, and noninvasive in vitro control of the motor units. PMID:27493991

  3. Vacuolar compartmentation of the cadmium-glutathione complex protects Saccharomyces cerevisiae from mutagenesis.

    PubMed

    Adamis, Paula D B; Panek, Anita D; Eleutherio, Elis C A

    2007-08-30

    In the yeast Saccharomyces cerevisiae, gamma-glutamyl transferase (gamma-GT; EC 2.3.2.2) is a vacuolar-membrane bound enzyme. In this work we verified that S. cerevisiae cells deficient in gamma-GT absorbed almost 2.5-fold as much cadmium as the wild-type (wt) cells, suggesting that this enzyme might be responsible for the recycle of cadmium-glutathione complex stored in the vacuole. The mutant strain showed difficulty in keeping constant levels of glutathione (GSH) during the stress, although the GSH-reductase activity was practically the same in both wt and mutant strains, before and after metal stress. This difficulty to maintain the GSH levels in the gamma-GT mutant strain led to high levels of lipid peroxidation and carbonyl proteins in response to cadmium, higher than in the wt, but lower than in a mutant deficient in GSH synthesis. Although the increased levels of oxidative stress, gamma-GT mutant strain showed to be tolerant to cadmium and showed similar mutation rates to the wt, indicating that the compartmentation of the GSH-cadmium complex in vacuole protects cells against the mutagenic action of the metal. Confirming this hypothesis, a mutant strain deficient in Ycf1, which present high concentrations of GSH-cadmium in cytoplasm due to its deficiency in transport the complex to vacuole, showed increased mutation rates. PMID:17644279

  4. Using pressure transient analysis to improve well performance and optimize field development in compartmentalized shelf margin deltaic reservoirs

    SciTech Connect

    Badgett, K.L.; Crawford, G.E.; Mills, W.H.

    1996-12-31

    BP Exploration`s Gulf of Mexico group developed procedures to conduct effective well tests on conventional production wells and employed them during the development drilling phase of the Mississippi Canyon 109 (MC109) field. Bottomhole pressure data were recorded during the initial few weeks of production. Typically, a 48 hour pressure buildup survey (surface shut-in) was obtained near the end of data acquisition. Data from these tests were analyzed for completion efficiency, reservoir flow capacity, reservoir heterogeneities, and drainage area. Initially wells were gravel packed for sand control, until buildup interpretations indicated skins greater than 20. Frac packing technology was then employed, and an immediate improvement was observed with skins dropping into the teens. Over a period of time frac packs were optimized using the test derived skins as a metric. Analysis of pressure data also played an important role in identifying reservoir compartmentalization. The two major reservoir horizons at MC 109 are interpreted as shelf margin deltas. However, each of these has distinctly different compartmentalization issues. The continuous character of the G Sand made it easier to define the depositional system and investigate reservoir compartmentalization issues using a combination of well log, 3D seismic, static pressure trends, and fluid information. In the more distal deltaic reservoirs of the J Sand however, complications with seismic amplitudes and a less reliable tie between wireline and seismic data required the use of pressure transient analysis to efficiently exploit the reservoir.

  5. Unchanged mitochondrial organization and compartmentation of high-energy phosphates in creatine-deficient GAMT−/− mouse hearts

    PubMed Central

    Branovets, Jelena; Sepp, Mervi; Kotlyarova, Svetlana; Jepihhina, Natalja; Sokolova, Niina; Aksentijevic, Dunja; Lygate, Craig A.; Neubauer, Stefan; Birkedal, Rikke

    2013-01-01

    Disruption of the creatine kinase (CK) system in hearts of CK-deficient mice leads to changes in the ultrastructure and regulation of mitochondrial respiration. We expected to see similar changes in creatine-deficient mice, which lack the enzyme guanidinoacetate methyltransferase (GAMT) to produce creatine. The aim of this study was to characterize the changes in cardiomyocyte mitochondrial organization, regulation of respiration, and intracellular compartmentation associated with GAMT deficiency. Three-dimensional mitochondrial organization was assessed by confocal microscopy. On populations of permeabilized cardiomyocytes, we recorded ADP and ATP kinetics of respiration, competition between mitochondria and pyruvate kinase for ADP produced by ATPases, ADP kinetics of endogenous pyruvate kinase, and ATP kinetics of ATPases. These data were analyzed by mathematical models to estimate intracellular compartmentation. Quantitative analysis of morphological and kinetic data as well as derived model fits showed no difference between GAMT-deficient and wild-type mice. We conclude that inactivation of the CK system by GAMT deficiency does not alter mitochondrial organization and intracellular compartmentation in relaxed cardiomyocytes. Thus, our results suggest that the healthy heart is able to preserve cardiac function at a basal level in the absence of CK-facilitated energy transfer without compromising intracellular organization and the regulation of mitochondrial energy homeostasis. This raises questions on the importance of the CK system as a spatial energy buffer in unstressed cardiomyocytes. PMID:23792673

  6. Action potential processing in a detailed Purkinje cell model reveals a critical role for axonal compartmentalization

    PubMed Central

    Masoli, Stefano; Solinas, Sergio; D'Angelo, Egidio

    2015-01-01

    The Purkinje cell (PC) is among the most complex neurons in the brain and plays a critical role for cerebellar functioning. PCs operate as fast pacemakers modulated by synaptic inputs but can switch from simple spikes to complex bursts and, in some conditions, show bistability. In contrast to original works emphasizing dendritic Ca-dependent mechanisms, recent experiments have supported a primary role for axonal Na-dependent processing, which could effectively regulate spike generation and transmission to deep cerebellar nuclei (DCN). In order to account for the numerous ionic mechanisms involved (at present including Nav1.6, Cav2.1, Cav3.1, Cav3.2, Cav3.3, Kv1.1, Kv1.5, Kv3.3, Kv3.4, Kv4.3, KCa1.1, KCa2.2, KCa3.1, Kir2.x, HCN1), we have elaborated a multicompartmental model incorporating available knowledge on localization and gating of PC ionic channels. The axon, including initial segment (AIS) and Ranvier nodes (RNs), proved critical to obtain appropriate pacemaking and firing frequency modulation. Simple spikes initiated in the AIS and protracted discharges were stabilized in the soma through Na-dependent mechanisms, while somato-dendritic Ca channels contributed to sustain pacemaking and to generate complex bursting at high discharge regimes. Bistability occurred only following Na and Ca channel down-regulation. In addition, specific properties in RNs K currents were required to limit spike transmission frequency along the axon. The model showed how organized electroresponsive functions could emerge from the molecular complexity of PCs and showed that the axon is fundamental to complement ionic channel compartmentalization enabling action potential processing and transmission of specific spike patterns to DCN. PMID:25759640

  7. Ultrafast Diffusion of a Fluorescent Cholesterol Analog in Compartmentalized Plasma Membranes

    PubMed Central

    Hiramoto-Yamaki, Nao; Tanaka, Kenji A K; Suzuki, Kenichi G N; Hirosawa, Koichiro M; Miyahara, Manami S H; Kalay, Ziya; Tanaka, Koichiro; Kasai, Rinshi S; Kusumi, Akihiro; Fujiwara, Takahiro K

    2014-01-01

    Cholesterol distribution and dynamics in the plasma membrane (PM) are poorly understood. The recent development of Bodipy488-conjugated cholesterol molecule (Bdp-Chol) allowed us to study cholesterol behavior in the PM, using single fluorescent-molecule imaging. Surprisingly, in the intact PM, Bdp-Chol diffused at the fastest rate ever found for any molecules in the PM, with a median diffusion coefficient (D) of 3.4 µm2/second, which was ∼10 times greater than that of non-raft phospholipid molecules (0.33 µm2/second), despite Bdp-Chol's probable association with raft domains. Furthermore, Bdp-Chol exhibited no sign of entrapment in time scales longer than 0.5 milliseconds. In the blebbed PM, where actin filaments were largely depleted, Bdp-Chol and Cy3-conjugated dioleoylphosphatidylethanolamine (Cy3-DOPE) diffused at comparable Ds (medians = 5.8 and 6.2 µm2/second, respectively), indicating that the actin-based membrane skeleton reduces the D of Bdp-Chol only by a factor of ∼2 from that in the blebbed PM, whereas it reduces the D of Cy3-DOPE by a factor of ∼20. These results are consistent with the previously proposed model, in which the PM is compartmentalized by the actin-based membrane-skeleton fence and its associated transmembrane picket proteins for the macroscopic diffusion of all of the membrane molecules, and suggest that the probability of Bdp-Chol passing through the compartment boundaries, once it enters the boundary, is ∼10× greater than that of Cy3-DOPE. Since the compartment sizes are greater than those of the putative raft domains, we conclude that raft domains coexist with membrane-skeleton-induced compartments and are contained within them. PMID:24506328

  8. A compartmental model to describe hydraulics in a full-scale waste stabilization pond.

    PubMed

    Alvarado, Andres; Vedantam, Sreepriya; Goethals, Peter; Nopens, Ingmar

    2012-02-01

    The advancement of experimental and computational resources has facilitated the use of computational fluid dynamics (CFD) models as a predictive tool for mixing behaviour in full-scale waste stabilization pond systems. However, in view of combining hydraulic behaviour with a biokinetic process model, the computational load is still too high for practical use. This contribution presents a method that uses a validated CFD model with tracer experiments as a platform for the development of a simpler compartmental model (CM) to describe the hydraulics in a full-scale maturation pond (7 ha) of a waste stabilization ponds complex in Cuenca (Ecuador). 3D CFD models were validated with experimental data from pulse tracer experiments, showing a sufficient agreement. Based on the CFD model results, a number of compartments were selected considering the turbulence characteristics of the flow, the residence time distribution (RTD) curves and the dominant velocity component at different pond locations. The arrangement of compartments based on the introduction of recirculation flow rate between adjacent compartments, which in turn is dependent on the turbulence diffusion coefficient, is illustrated. Simulated RTD's from a systemic tanks-in-series (TIS) model and the developed CM were compared. The TIS was unable to capture the measured RTD, whereas the CM predicted convincingly the peaks and lags of the tracer experiment using only a minimal fraction of the computational demand of the CFD model. Finally, a biokinetic model was coupled to both approaches demonstrating the impact an insufficient hydraulic model can have on the outcome of a modelling exercise. TIS and CM showed drastic differences in the output loads implying that the CM approach is to be used when modelling the biological performance of the full-scale system. PMID:22137448

  9. Subsurface fluid data from Longyearbyen CO2 storage site: Basin history and compartmentalization

    NASA Astrophysics Data System (ADS)

    Huq, Farhana; Mueller, Kristin; Tore Mørkved, Pål; Johansen, Ingar; Johansen, Harald

    2015-04-01

    The Longyearbyen CO2 storage site, located on the main island of Svalbard at the northwestern margin of the Barents Sea Shelf, is a demonstration project for a "green showcase", which aims to make a full value chain of power generation, CO2 capture and storage by achieving a net zero carbon footprint. The key objective of this study was to assess the local geological conditions for CO2 storage by defining a seal sequence stratigraphy above and within the reservoir from gas and fluid geochemical data. Seven wells were drilled at two sites to collect core material and gas samples at various defined depths. Gas composition (C1-5, CO2) and stable isotope (δ13C) analyses were performed on gas samples obtained from both core material and well heads. In addition, Sr isotope data from residual salts extracted from core material were used to look at compartmentalization. The combined analysis of trends in isotope and gas composition data as a function of depth revealed three major breaks and permitted the identification of three major fluid compartments. These compartments are suggested to be associated with impervious caprock and reservoir barriers. The first break in the data trends occurs at approximately 250-300 m depth, which is interpreted as the depth limit of the meteoric water system. A second hydrologic barrier, most likely produced by reservoir uplift was identified. Finally, a very distinct change in trend around 800 m depth may be associated with an observed significant change in reservoir pressure. Three clear breaks in the geochemical data as a function of depth all point towards an efficient seal sequence and demonstrate the potential for CO2 storage at the Longyearbyen site.

  10. Compartmentation of the cerebellar cortex: adaptation to lifestyle in the star-nosed mole Condylura cristata.

    PubMed

    Marzban, Hassan; Hoy, Nathan; Buchok, Matthew; Catania, Kenneth C; Hawkes, Richard

    2015-04-01

    The adult mammalian cerebellum is histologically uniform. However, concealed beneath the simple laminar architecture, it is organized rostrocaudally and mediolaterally into complex arrays of transverse zones and parasagittal stripes that is both highly reproducible between individuals and generally conserved across mammals and birds. Beyond this conservation, the general architecture appears to be adapted to the animal's way of life. To test this hypothesis, we have examined cerebellar compartmentation in the talpid star-nosed mole Condylura cristata. The star-nosed mole leads a subterranean life. It is largely blind and instead uses an array of fleshy appendages (the "star") to navigate and locate its prey. The hypothesis suggests that cerebellar architecture would be modified to reduce regions receiving visual input and expand those that receive trigeminal afferents from the star. Zebrin II and phospholipase Cß4 (PLCß4) immunocytochemistry was used to map the zone-and-stripe architecture of the cerebellum of the adult star-nosed mole. The general zone-and-stripe architecture characteristic of all mammals is present in the star-nosed mole. In the vermis, the four typical transverse zones are present, two with alternating zebrin II/PLCß4 stripes, two wholly zebrin II+/PLCß4-. However, the central and nodular zones (prominent visual receiving areas) are proportionally reduced in size and conversely, the trigeminal-receiving areas (the posterior zone of the vermis and crus I/II of the hemispheres) are uncharacteristically large. We therefore conclude that cerebellar architecture is generally conserved across the Mammalia but adapted to the specific lifestyle of the species. PMID:25337886

  11. Structural compartmentalization in a decapitated anticline: The example of the Divide Creek fractured reservoir, Piceance Basin

    SciTech Connect

    Hoak, T.E.; Klawitter, A.L. )

    1996-01-01

    Integrated analysis of high-resolution aeromagnetic and remote sensing data, confirmed by field geology, seismic and production data, demonstrates reservoir compartmentalization within the Divide Creek Field, southeast Piceance Basin. Topographic constraints and Federal land use restrictions, limit the ability to collect extensive seismic data across this complex structure and precludes complete characterization of subsurface structure by direct methods. Integrated analysis of airborne aeromagnetic data with TM (thematic mapper) and SAR (synthetic aperture radar) data, permit the resolution of the 3D complexity of this fold and its associated reservoir not easily defined using conventional 2D seismic. The Divide Creek Anticline is a decapitated pop-up anticline. The pop-up anticline that originally formed along a deeper, Eagle Valley Evaporite detachment surface has been [open quotes]decapitated[close quotes] along a shallower Manoos-level detachment that translates the shallows pop-up anticlinal axis to the west. The fold is further segmented by normal faults trending axis-perpendicular to its axis that create distinct reservoir compartments. Processing of aeromagnetic data using multiple bandpass filters demonstrates three detachments in the fold, and the 3D geometry of the detachments. Understanding timing of these structures is critical for constraining fracture genesis and gas migration models, Oriented fracture data from surficial studies, aeromagnetic data, remote sensing imagery, and subsurface core delineated three primary trends. These trends correspond to axis-parallel, axis-perpendicular and an older oblique regional fracture sets. This fracture permeability has made Divide Creek Field the most prolific Piceance Basin tight gas sand field.

  12. Structural compartmentalization in a decapitated anticline: The example of the Divide Creek fractured reservoir, Piceance Basin

    SciTech Connect

    Hoak, T.E.; Klawitter, A.L.

    1996-12-31

    Integrated analysis of high-resolution aeromagnetic and remote sensing data, confirmed by field geology, seismic and production data, demonstrates reservoir compartmentalization within the Divide Creek Field, southeast Piceance Basin. Topographic constraints and Federal land use restrictions, limit the ability to collect extensive seismic data across this complex structure and precludes complete characterization of subsurface structure by direct methods. Integrated analysis of airborne aeromagnetic data with TM (thematic mapper) and SAR (synthetic aperture radar) data, permit the resolution of the 3D complexity of this fold and its associated reservoir not easily defined using conventional 2D seismic. The Divide Creek Anticline is a decapitated pop-up anticline. The pop-up anticline that originally formed along a deeper, Eagle Valley Evaporite detachment surface has been {open_quotes}decapitated{close_quotes} along a shallower Manoos-level detachment that translates the shallows pop-up anticlinal axis to the west. The fold is further segmented by normal faults trending axis-perpendicular to its axis that create distinct reservoir compartments. Processing of aeromagnetic data using multiple bandpass filters demonstrates three detachments in the fold, and the 3D geometry of the detachments. Understanding timing of these structures is critical for constraining fracture genesis and gas migration models, Oriented fracture data from surficial studies, aeromagnetic data, remote sensing imagery, and subsurface core delineated three primary trends. These trends correspond to axis-parallel, axis-perpendicular and an older oblique regional fracture sets. This fracture permeability has made Divide Creek Field the most prolific Piceance Basin tight gas sand field.

  13. Role of Membrane Microdomains in Compartmentation of cAMP Signaling

    PubMed Central

    Agarwal, Shailesh R.; Yang, Pei-Chi; Rice, Monica; Singer, Cherie A.; Nikolaev, Viacheslav O.; Lohse, Martin J.; Clancy, Colleen E.; Harvey, Robert D.

    2014-01-01

    Spatially restricting cAMP production to discrete subcellular locations permits selective regulation of specific functional responses. But exactly where and how cAMP signaling is confined is not fully understood. Different receptors and adenylyl cyclase isoforms responsible for cAMP production are not uniformly distributed between lipid raft and non-lipid raft domains of the plasma membrane. We sought to determine the role that these membrane domains play in organizing cAMP responses in HEK293 cells. The freely diffusible FRET-based biosensor Epac2-camps was used to measure global cAMP responses, while versions of the probe targeted to lipid raft (Epac2-MyrPalm) and non-raft (Epac2-CAAX) domains were used to monitor local cAMP production near the plasma membrane. Disruption of lipid rafts by cholesterol depletion selectively altered cAMP responses produced by raft-associated receptors. The results indicate that receptors associated with lipid raft as well as non-lipid raft domains can contribute to global cAMP responses. In addition, basal cAMP activity was found to be significantly higher in non-raft domains. This was supported by the fact that pharmacologic inhibition of adenylyl cyclase activity reduced basal cAMP activity detected by Epac2-CAAX but not Epac2-MyrPalm or Epac2-camps. Responses detected by Epac2-CAAX were also more sensitive to direct stimulation of adenylyl cyclase activity, but less sensitive to inhibition of phosphodiesterase activity. Quantitative modeling was used to demonstrate that differences in adenylyl cyclase and phosphodiesterase activities are necessary but not sufficient to explain compartmentation of cAMP associated with different microdomains of the plasma membrane. PMID:24752595

  14. Compartmentalized cyanophycin metabolism in the diazotrophic filaments of a heterocyst-forming cyanobacterium

    PubMed Central

    Burnat, Mireia; Herrero, Antonia; Flores, Enrique

    2014-01-01

    Heterocyst-forming cyanobacteria are multicellular organisms in which growth requires the activity of two metabolically interdependent cell types, the vegetative cells that perform oxygenic photosynthesis and the dinitrogen-fixing heterocysts. Vegetative cells provide the heterocysts with reduced carbon, and heterocysts provide the vegetative cells with fixed nitrogen. Heterocysts conspicuously accumulate polar granules made of cyanophycin [multi-L-arginyl-poly (L-aspartic acid)], which is synthesized by cyanophycin synthetase and degraded by the concerted action of cyanophycinase (that releases β-aspartyl-arginine) and isoaspartyl dipeptidase (that produces aspartate and arginine). Cyanophycin synthetase and cyanophycinase are present at high levels in the heterocysts. Here we created a deletion mutant of gene all3922 encoding isoaspartyl dipeptidase in the model heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120. The mutant accumulated cyanophycin and β-aspartyl-arginine, and was impaired specifically in diazotrophic growth. Analysis of an Anabaena strain bearing an All3922-GFP (green fluorescent protein) fusion and determination of the enzyme activity in specific cell types showed that isoaspartyl dipeptidase is present at significantly lower levels in heterocysts than in vegetative cells. Consistently, isolated heterocysts released substantial amounts of β-aspartyl-arginine. These observations imply that β-aspartyl-arginine produced from cyanophycin in the heterocysts is transferred intercellularly to be hydrolyzed, producing aspartate and arginine in the vegetative cells. Our results showing compartmentalized metabolism of cyanophycin identify the nitrogen-rich molecule β-aspartyl-arginine as a nitrogen vehicle in the unique multicellular system represented by the heterocyst-forming cyanobacteria. PMID:24550502

  15. Distribution and compartmental organization of GABAergic medium-sized spiny neurons in the mouse nucleus accumbens

    PubMed Central

    Gangarossa, Giuseppe; Espallergues, Julie; de Kerchove d'Exaerde, Alban; El Mestikawy, Salah; Gerfen, Charles R.; Hervé, Denis; Girault, Jean-Antoine; Valjent, Emmanuel

    2012-01-01

    The nucleus accumbens (NAc) is a critical brain region involved in many reward-related behaviors. The NAc comprises major compartments the core and the shell, which encompass several subterritories. GABAergic medium-sized spiny neurons (MSNs) constitute the output neurons of the NAc core and shell. While the functional organization of the NAc core outputs resembles the one described for the dorsal striatum, a simple classification of the NAc shell neurons has been difficult to define due to the complexity of the compartmental segregation of cells. We used a variety of BAC transgenic mice expressing enhanced green fluorescence (EGFP) or the Cre-recombinase (Cre) under the control of the promoter of dopamine D1, D2, and D3 receptors and of adenosine A2a receptor to dissect the microanatomy of the NAc. Moreover, using various immunological markers we characterized in detail the distribution of MSNs in the mouse NAc. In addition, cell-type specific extracellular signal-regulated kinase (ERK) phosphorylation in the NAc subterritories was analyzed following acute administration of SKF81297 (a D1R-like agonist), quinpirole (a D2 receptors (D2R)-like agonist), apomorphine (a non-selective DA receptor agonist), raclopride (a D2R-like antagonist), and psychostimulant drugs, including cocaine and d-amphetamine. Each drug generated a unique topography and cell-type specific activation of ERK in the NAc. Our results show the existence of marked differences in the receptor expression pattern and functional activation of MSNs within the shell subterritories. This study emphasizes the anatomical and functional heterogeneity of the NAc, which will have to be considered in its further study. PMID:23423476

  16. Distribution and compartmental organization of GABAergic medium-sized spiny neurons in the mouse nucleus accumbens.

    PubMed

    Gangarossa, Giuseppe; Espallergues, Julie; de Kerchove d'Exaerde, Alban; El Mestikawy, Salah; Gerfen, Charles R; Hervé, Denis; Girault, Jean-Antoine; Valjent, Emmanuel

    2013-01-01

    The nucleus accumbens (NAc) is a critical brain region involved in many reward-related behaviors. The NAc comprises major compartments the core and the shell, which encompass several subterritories. GABAergic medium-sized spiny neurons (MSNs) constitute the output neurons of the NAc core and shell. While the functional organization of the NAc core outputs resembles the one described for the dorsal striatum, a simple classification of the NAc shell neurons has been difficult to define due to the complexity of the compartmental segregation of cells. We used a variety of BAC transgenic mice expressing enhanced green fluorescence (EGFP) or the Cre-recombinase (Cre) under the control of the promoter of dopamine D1, D2, and D3 receptors and of adenosine A2a receptor to dissect the microanatomy of the NAc. Moreover, using various immunological markers we characterized in detail the distribution of MSNs in the mouse NAc. In addition, cell-type specific extracellular signal-regulated kinase (ERK) phosphorylation in the NAc subterritories was analyzed following acute administration of SKF81297 (a D1R-like agonist), quinpirole (a D2 receptors (D2R)-like agonist), apomorphine (a non-selective DA receptor agonist), raclopride (a D2R-like antagonist), and psychostimulant drugs, including cocaine and d-amphetamine. Each drug generated a unique topography and cell-type specific activation of ERK in the NAc. Our results show the existence of marked differences in the receptor expression pattern and functional activation of MSNs within the shell subterritories. This study emphasizes the anatomical and functional heterogeneity of the NAc, which will have to be considered in its further study. PMID:23423476

  17. Compartmentalization of stearoyl-coenzyme A desaturase 1 activity in HepG2 cells*

    PubMed Central

    Yee, Jennifer K.; Mao, Catherine S.; Hummel, Heidi S.; Lim, Shu; Sugano, Sharon; Rehan, Virender K.; Xiao, Gary; Lee, Wai-Nang Paul

    2008-01-01

    Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the conversion of stearate (18:0) to oleate (18:1n-9) and of palmitate (16:0) to palmitoleate (16:1), which are key steps in triglyceride synthesis in the fatty acid metabolic network. This study investigated the role of SCD1 in fatty acid metabolism in HepG2 cells using SCD1 inhibitors and stable isotope tracers. HepG2 cells were cultured with [U-13C]stearate, [U-13C]palmitate, or [1,2-13C]acetate and (1) DMSO, (2) compound CGX0168 or CGX0290, or (3) trans-10,cis-12 conjugated linoleic acid (CLA). 13C incorporation into fatty acids was determined by GC-MS and desaturation indices calculated from the respective ion chromatograms. FAS, SCD1, peroxisome proliferator-activated receptor α, and peroxisome proliferator-activated receptor γ mRNA levels were assessed by semiquantitative RT-PCR. The addition of CGX0168 and CGX0290 decreased the stearate and palmitate desaturation indices in HepG2 cells. CLA led to a decrease in the desaturation of stearate only, but not palmitate. Comparison of desaturation indices based on isotope enrichment ratios differed, depending on the origin of saturated fatty acid. SCD1 gene expression was not affected in any group. In conclusion, the differential effects of SCD1 inhibitors and CLA on SCD1 activity combined with the dependence of desaturation indices on the source of saturated fatty acid strongly support the compartmentalization of desaturation systems. The effects of SCD1 inhibition on fatty acid composition in HepG2 cells occurred through changes in the dynamics of the fatty acid metabolic network and not through transcriptional regulatory mechanisms. PMID:18599738

  18. Convex-Optimization-Based Compartmental Pharmacokinetic Analysis for Prostate Tumor Characterization Using DCE-MRI.

    PubMed

    Ambikapathi, ArulMurugan; Chan, Tsung-Han; Lin, Chia-Hsiang; Yang, Fei-Shih; Chi, Chong-Yung; Wang, Yue

    2016-04-01

    Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a powerful imaging modality to study the pharmacokinetics in a suspected cancer/tumor tissue. The pharmacokinetic (PK) analysis of prostate cancer includes the estimation of time activity curves (TACs), and thereby, the corresponding kinetic parameters (KPs), and plays a pivotal role in diagnosis and prognosis of prostate cancer. In this paper, we endeavor to develop a blind source separation algorithm, namely convex-optimization-based KPs estimation (COKE) algorithm for PK analysis based on compartmental modeling of DCE-MRI data, for effective prostate tumor detection and its quantification. The COKE algorithm first identifies the best three representative pixels in the DCE-MRI data, corresponding to the plasma, fast-flow, and slow-flow TACs, respectively. The estimation accuracy of the flux rate constants (FRCs) of the fast-flow and slow-flow TACs directly affects the estimation accuracy of the KPs that provide the cancer and normal tissue distribution maps in the prostate region. The COKE algorithm wisely exploits the matrix structure (Toeplitz, lower triangular, and exponential decay) of the original nonconvex FRCs estimation problem, and reformulates it into two convex optimization problems that can reliably estimate the FRCs. After estimation of the FRCs, the KPs can be effectively estimated by solving a pixel-wise constrained curve-fitting (convex) problem. Simulation results demonstrate the efficacy of the proposed COKE algorithm. The COKE algorithm is also evaluated with DCE-MRI data of four different patients with prostate cancer and the obtained results are consistent with clinical observations. PMID:26292336

  19. Consequences of plant invasions on compartmentalization and species’ roles in plant–pollinator networks

    PubMed Central

    Albrecht, Matthias; Padrón, Benigno; Bartomeus, Ignasi; Traveset, Anna

    2014-01-01

    Compartmentalization—the organization of ecological interaction networks into subsets of species that do not interact with other subsets (true compartments) or interact more frequently among themselves than with other species (modules)—has been identified as a key property for the functioning, stability and evolution of ecological communities. Invasions by entomophilous invasive plants may profoundly alter the way interaction networks are compartmentalized. We analysed a comprehensive dataset of 40 paired plant–pollinator networks (invaded versus uninvaded) to test this hypothesis. We show that invasive plants have higher generalization levels with respect to their pollinators than natives. The consequences for network topology are that—rather than displacing native species from the network—plant invaders attracting pollinators into invaded modules tend to play new important topological roles (i.e. network hubs, module hubs and connectors) and cause role shifts in native species, creating larger modules that are more connected among each other. While the number of true compartments was lower in invaded compared with uninvaded networks, the effect of invasion on modularity was contingent on the study system. Interestingly, the generalization level of the invasive plants partially explains this pattern, with more generalized invaders contributing to a lower modularity. Our findings indicate that the altered interaction structure of invaded networks makes them more robust against simulated random secondary species extinctions, but more vulnerable when the typically highly connected invasive plants go extinct first. The consequences and pathways by which biological invasions alter the interaction structure of plant–pollinator communities highlighted in this study may have important dynamical and functional implications, for example, by influencing multi-species reciprocal selection regimes and coevolutionary processes. PMID:24943368

  20. Purkinje cell compartmentalization in the cerebellum of the spontaneous mutant mouse dreher

    PubMed Central

    Sillitoe, Roy V.; George-Jones, Nicholas A.; Millen, Kathleen J.; Hawkes, Richard

    2014-01-01

    The cerebellar morphological phenotype of the spontaneous neurological mutant mouse dreher (Lmx1adr-J) results from cell fate changes in dorsal midline patterning involving the roof plate and rhombic lip. Positional cloning revealed that the gene Lmx1a, which encodes a LIM homeodomain protein, is mutated in dreher, and is expressed in the developing roof plate and rhombic lip. Loss of Lmx1a causes reduction of the roof plate, an important embryonic signaling center, and abnormal cell fate specification within the embryonic cerebellar rhombic lip. In adult animals, these defects result in variable, medial fusion of the cerebellar vermis and posterior cerebellar vermis hypoplasia. It is unknown whether deleting Lmx1a results in displacement or loss of specific lobules in the vermis. To distinguish between an ectopic and an absent vermis, the expression patterns of two Purkinje cell specific compartmentation antigens, zebrin II/aldolase C and the small heat shock protein HSP25, were analyzed in dreher cerebella. The data reveal that despite the reduction in volume and abnormal foliation of the cerebellum, the transverse zones and parasagittal stripe arrays characteristic of the normal vermis are present in dreher, but may be highly distorted. In dreher mutants with a severe phenotype, zebrin II stripes are fragmented and distributed non-symmetrically about the cerebellar midline. We conclude that although Purkinje cell agenesis or selective Purkinje cell death may contribute to the dreher phenotype, our data suggest that aberrant anlage patterning and granule cell development lead to Purkinje cell ectopia, which ultimately causes abnormal cerebellar architecture in dreher. PMID:23160833

  1. Heterodinuclear Ln[bond]Na complexes with an asymmetrical macrocyclic compartmental Schiff base.

    PubMed

    Bottamauro, Mauro; Casellato, Umberto; Scalco, Cristina; Tamburini, Sergio; Tomasin, Patrizi; Vigato, Pietro A; Aime, Silvio; Barge, Alessandro

    2002-09-01

    Heterodinuclear lanthanide(III)-sodium(I) complexes [LnNa(L)(Cl)(2)(CH(3)OH)] (Ln=La[bond]Nd, Sm[bond]Lu), where H(2)L is a [1+1] asymmetric compartmental macrocyclic ligand containing a N(3)O(2) Schiff base and a O(3)O(2) crown-ether-like coordination site, have been prepared and characterized by IR, (1)H, (13)C, and (23)Na NMR spectroscopy, mass spectrometry, and electron microscopy. In the solid state, the lanthanide(III) ions coordinate the Schiff-base N(3)O(2) site, and the sodium ion occupies the O(3)O(2) crownlike cavity, as shown by the X-ray crystal structures of the Nd, Eu, Gd, and Yb derivatives. In these complexes, the lanthanide(III) ion is coordinated by two chlorine atoms in the trans position and by three nitrogen and two negatively charged phenol oxygen atoms of the Schiff base, and the ion is heptacoordinated with a pentagonal bipyramidal geometry. The sodium ion is coordinated by three etheric oxygen atoms and the two phenolic oxygens that act as a bridge. A methanol molecule is also coordinated in the apical position of the resulting pentagonal pyramidal polyhedron. A detailed (1)H and (13)C NMR study was carried out in CD(3)OD for both diamagnetic and paramagnetic heterodinuclear complexes [LnNa(L)(Cl)(2)(CH(3)OH)]. The complexes are also isostructural in solution, and their structures parallel those found in the solid state. Moreover, some significative distances determined in the solid state and in solution are comparable. Finally, the potential use of these complexes as molecular probes for the selective recognition of specific metal ions has been tested. In particular, their ability to act as shift reagents and the selectivity of the O(3)O(2) site towards Li(+), Ca(2+), and K(+) were investigated by (23)Na NMR spectroscopy. PMID:12360933

  2. Retinol metabolism in rats with low vitamin A status: A compartmental model

    SciTech Connect

    Lewis, K.C.; Green, M.H.; Green, J.B.; Zech, L.A. )

    1990-09-01

    A compartmental model was developed to describe the metabolism of vitamin A in rats with low vitamin A status maintained by a low dietary intake of vitamin A (approximately 2 micrograms retinol equivalents/day). After the IV bolus injection of (3H)retinol in its physiological transport complex, tracer and trace data were obtained from plasma, organs (liver, kidneys, small intestine, eyes, adrenals, testes, lungs, carcass), and tracer data were obtained from urine and feces. The dietary protocol developed for this study resulted in animals having plasma vitamin A levels less than 10 micrograms retinol/dl and total liver vitamin A levels of approximately 1 microgram retinol equivalent. Four compartments were used to model the plasma: one to describe retinol, one to describe the nonphysiological portion of the dose, and two to simulate polar metabolites derived from retinol. The liver required two compartments and a delay, the carcass (small intestine, eyes, adrenals, testes, and lungs, plus remaining carcass) required three compartments, and the kidneys required two. The model predicted a vitamin A utilization rate of 1.65 micrograms retinol equivalents/day with the urine and feces accounting for most of the output. The plasma retinol turnover rate was approximately 20 micrograms retinol equivalents/day; this was 12 times greater than the utilization rate. This indicated that, of the large amount of retinol moving through the plasma each day, less than 10% of this was actually being irreversibly utilized. Similarly, as compared to the whole-body utilization rate, there was a relatively high turnover rate of retinol in the kidneys, carcass, and liver, coupled with a high degree of recycling of vitamin A through these tissues. Of the total vitamin A that entered the liver from all sources including the diet, approximately 86% was mobilized into the plasma.

  3. Compartmentalized Ras Proteins Transform NIH 3T3 Cells with Different Efficiencies▿ †

    PubMed Central

    Cheng, Chiang-Min; Li, Huiling; Gasman, Stéphane; Huang, Jian; Schiff, Rachel; Chang, Eric C.

    2011-01-01

    Ras GTPases were long thought to function exclusively from the plasma membrane (PM). However, a current model suggests that Ras proteins can compartmentalize to regulate different functions, and an oncogenic H-Ras mutant that is restricted to the endomembrane can still transform cells. In this study, we demonstrated that cells transformed by endomembrane-restricted oncogenic H-Ras formed tumors in nude mice. To define downstream targets of endomembrane Ras pathways, we analyzed Cdc42, which concentrates in the endomembrane and has been shown to act downstream of Ras in Schizosaccharomyces pombe. Our data show that cell transformation induced by endomembrane-restricted oncogenic H-Ras was blocked when Cdc42 activity was inhibited. Moreover, H-Ras formed a complex with Cdc42 on the endomembrane, and this interaction was enhanced when H-Ras was GTP bound or when cells were stimulated by growth factors. H-Ras binding evidently induced Cdc42 activation by recruiting and/or activating Cdc42 exchange factors. In contrast, when constitutively active H-Ras was restricted to the PM by fusing to a PM localization signal from the Rit GTPase, the resulting protein did not detectably activate Cdc42 although it activated Raf-1 and efficiently induced hallmarks of Ras-induced senescence in human BJ foreskin fibroblasts. Surprisingly, PM-restricted oncogenic Ras when expressed alone could only weakly transform NIH 3T3 cells; however, when constitutively active Cdc42 was coexpressed, together they transformed cells much more efficiently than either one alone. These data suggest that efficient cell transformation requires Ras proteins to interact with Cdc42 on the endomembrane and that in order for a given Ras protein to fully transform cells, multiple compartment-specific Ras pathways need to work cooperatively. PMID:21189290

  4. Compartmental bone morphometry in the mouse femur: reproducibility and resolution dependence of microtomographic measurements.

    PubMed

    Kohler, T; Beyeler, M; Webster, D; Müller, R

    2005-11-01

    Microcomputed tomography (microCT) is widely used for nondestructive bone phenotyping in small animals, especially in the mouse. Here, we investigated the reproducibility and resolution dependence of microCT analysis of microstructural parameters in three different compartments in the mouse femur. Reproducibility was assessed with respect to precision error (PE%CV) and intraclass correlation coefficient (ICC). We examined 14 left femurs isolated postmortem from two strains of mice (seven per group). Measurements and analyses were repeated five times on different days. In a second step, analysis was repeated again five times for a single measurement. Resolution dependence was assessed by high-resolution measurements (10 microm) in one strain and subsequent image degrading. Reproducibility was better in full bone compartment and in cortical bone compartment in the diaphysis (PE%CV = 0.06-2.16%) than in trabecular compartment in the distal metaphysis (PE(%CV) = 0.59-5.24%). Nevertheless, ICC (0.92-1.00) showed a very high reliability of the assessed parameters in all regions, indicating very small variances within repeated measurements compared to the population variances. Morphometric indices computed from lower- and higher-resolution images displayed in general only weak dependence and were highly correlated with each other (R2 = 0.91-0.99). The results show that parameters in the full and cortical compartments were very reproducible, whereas precision in the trabecular compartment was somewhat lower. Nevertheless, all compartmental analysis methods were very robust, as shown by the high ICC values, demonstrating high suitability for application in inbred strains, where highest precision is needed due to small population variances. PMID:16283571

  5. Nuclear envelope morphology constrains diffusion and promotes asymmetric protein segregation in closed mitosis

    PubMed Central

    Boettcher, Barbara; Marquez-Lago, Tatiana T.; Bayer, Mathias; Weiss, Eric L.

    2012-01-01

    During vegetative growth, Saccharomyces cerevisiae cells divide asymmetrically: the mother cell buds to produce a smaller daughter cell. This daughter asymmetrically inherits the transcription factor Ace2, which activates daughter-specific transcriptional programs. In this paper, we investigate when and how this asymmetry is established and maintained. We show that Ace2 asymmetry is initiated in the elongated, but undivided, anaphase nucleus. At this stage, the nucleoplasm was highly compartmentalized; little exchange was observed for nucleoplasmic proteins between mother and bud. Using photobleaching and in silico modeling, we show that diffusion barriers compartmentalize the nuclear membranes. In contrast, the behavior of proteins in the nucleoplasm is well explained by the dumbbell shape of the anaphase nucleus. This compartmentalization of the nucleoplasm promoted Ace2 asymmetry in anaphase nuclei. Thus, our data indicate that yeast cells use the process of closed mitosis and the morphological constraints associated with it to asymmetrically segregate nucleoplasmic components. PMID:22711697

  6. Purkinje Cell Compartmentation in the Cerebellum of the Lysosomal Acid Phosphatase 2 Mutant Mouse (Nax - Naked-Ataxia Mutant Mouse)

    PubMed Central

    Bailey, Karen; Rahimi Balaei, Maryam; Mannan, Ashraf; Del Bigio, Marc R.; Marzban, Hassan

    2014-01-01

    The Acp2 gene encodes the beta subunit of lysosomal acid phosphatase, which is an isoenzyme that hydrolyzes orthophosphoric monoesters. In mice, a spontaneous mutation in Acp2 results in severe cerebellar defects. These include a reduced size, abnormal lobulation, and an apparent anterior cerebellar disorder with an absent or hypoplastic vermis. Based on differential gene expression in the cerebellum, the mouse cerebellar cortex can normally be compartmentalized anteroposteriorly into four transverse zones and mediolaterally into parasagittal stripes. In this study, immunohistochemistry was performed using various Purkinje cell compartmentation markers to examine their expression patterns in the Acp2 mutant. Despite the abnormal lobulation and anterior cerebellar defects, zebrin II and PLCβ4 showed similar expression patterns in the nax mutant and wild type cerebellum. However, fewer stripes were found in the anterior zone of the nax mutant, which could be due to a lack of Purkinje cells or altered expression of the stripe markers. HSP25 expression was uniform in the central zone of the nax mutant cerebellum at around postnatal day (P) 18–19, suggesting that HSP25 immunonegative Purkinje cells are absent or delayed in stripe pattern expression compared to the wild type. HSP25 expression became heterogeneous around P22–23, with twice the number of parasagittal stripes in the nax mutant compared to the wild type. Aside from reduced size and cortical disorganization, both the posterior zone and nodular zone in the nax mutant appeared less abnormal than the rest of the cerebellum. From these results, it is evident that the anterior zone of the nax mutant cerebellum is the most severely affected, and this extends beyond the primary fissure into the rostral central zone/vermis. This suggests that ACP2 has critical roles in the development of the anterior cerebellum and it may regulate anterior and central zone compartmentation. PMID:24722417

  7. Sequence stratigraphic and synsedimentary tectonic controls on reservoir compartmentalization in a transgressive sequence set: Almond formation, southwest Wyoming

    SciTech Connect

    Krystinik, L.F.; Mead, R.H. )

    1996-01-01

    The Campanian upper Almond Formation in Southwestern Wyoming contains at least 15 aggradational to backstepping microtidal to low mesotidal barrier/shoreline complexes laid down during a period of net transgression from 72 to 70.5 million years ago. Reservoir compartmentalization in the upper Almond occurs at several scales, including an aggradational to retrogradations sequence set composed of 3 retrogradational parasequence sets; numerous parasequences, and diverse barrier sub-facies units. The lowstand shorelines of these sequence sets stack aggradationally prior to transgression by a really extensive, marine mudstone horizons which separate the sequences. Highstand systems tracts are poorly preserved, often completely removed below fourth of fifth order sequence boundaries which cause seaward jumps of facies in excess of 30 Km and place fluvial sediment, coal and lagoonal deposits abruptly over marine mudstone. Each sequence in the upper Almond is composed of several parasequences (sanding-upward, storm-dominated barrier shorefaces) which intercalate with marine mudstone to the east and grade into oyster-bearing, organic-rich lagoonal mudstone to the west. Compartmentalization in the barrier complexes occurs at most parasequence boundaries and in association with major sub-facies; boundaries (barrier margins, tidal inlets, flood-tidal deltas, washover fans). Further reservoir compartmentalization is induced by synsedimentary faulting and subsidence which locally preserve isolated reservoir-quality barrier/shoreline sandstone bodies by dropping them below the depth of ravinement (5-30 m). The recognition of synsedimentary faulting and subsequent ravinement is critical to accurate sequence stratigraphic analysis and for prediction of reservoir compartments.

  8. Sequence stratigraphic and synsedimentary tectonic controls on reservoir compartmentalization in a transgressive sequence set: Almond formation, southwest Wyoming

    SciTech Connect

    Krystinik, L.F.; Mead, R.H.

    1996-12-31

    The Campanian upper Almond Formation in Southwestern Wyoming contains at least 15 aggradational to backstepping microtidal to low mesotidal barrier/shoreline complexes laid down during a period of net transgression from 72 to 70.5 million years ago. Reservoir compartmentalization in the upper Almond occurs at several scales, including an aggradational to retrogradations sequence set composed of 3 retrogradational parasequence sets; numerous parasequences, and diverse barrier sub-facies units. The lowstand shorelines of these sequence sets stack aggradationally prior to transgression by a really extensive, marine mudstone horizons which separate the sequences. Highstand systems tracts are poorly preserved, often completely removed below fourth of fifth order sequence boundaries which cause seaward jumps of facies in excess of 30 Km and place fluvial sediment, coal and lagoonal deposits abruptly over marine mudstone. Each sequence in the upper Almond is composed of several parasequences (sanding-upward, storm-dominated barrier shorefaces) which intercalate with marine mudstone to the east and grade into oyster-bearing, organic-rich lagoonal mudstone to the west. Compartmentalization in the barrier complexes occurs at most parasequence boundaries and in association with major sub-facies; boundaries (barrier margins, tidal inlets, flood-tidal deltas, washover fans). Further reservoir compartmentalization is induced by synsedimentary faulting and subsidence which locally preserve isolated reservoir-quality barrier/shoreline sandstone bodies by dropping them below the depth of ravinement (5-30 m). The recognition of synsedimentary faulting and subsequent ravinement is critical to accurate sequence stratigraphic analysis and for prediction of reservoir compartments.

  9. Purkinje cell compartmentation in the cerebellum of the lysosomal Acid phosphatase 2 mutant mouse (nax - naked-ataxia mutant mouse).

    PubMed

    Bailey, Karen; Rahimi Balaei, Maryam; Mannan, Ashraf; Del Bigio, Marc R; Marzban, Hassan

    2014-01-01

    The Acp2 gene encodes the beta subunit of lysosomal acid phosphatase, which is an isoenzyme that hydrolyzes orthophosphoric monoesters. In mice, a spontaneous mutation in Acp2 results in severe cerebellar defects. These include a reduced size, abnormal lobulation, and an apparent anterior cerebellar disorder with an absent or hypoplastic vermis. Based on differential gene expression in the cerebellum, the mouse cerebellar cortex can normally be compartmentalized anteroposteriorly into four transverse zones and mediolaterally into parasagittal stripes. In this study, immunohistochemistry was performed using various Purkinje cell compartmentation markers to examine their expression patterns in the Acp2 mutant. Despite the abnormal lobulation and anterior cerebellar defects, zebrin II and PLCβ4 showed similar expression patterns in the nax mutant and wild type cerebellum. However, fewer stripes were found in the anterior zone of the nax mutant, which could be due to a lack of Purkinje cells or altered expression of the stripe markers. HSP25 expression was uniform in the central zone of the nax mutant cerebellum at around postnatal day (P) 18-19, suggesting that HSP25 immunonegative Purkinje cells are absent or delayed in stripe pattern expression compared to the wild type. HSP25 expression became heterogeneous around P22-23, with twice the number of parasagittal stripes in the nax mutant compared to the wild type. Aside from reduced size and cortical disorganization, both the posterior zone and nodular zone in the nax mutant appeared less abnormal than the rest of the cerebellum. From these results, it is evident that the anterior zone of the nax mutant cerebellum is the most severely affected, and this extends beyond the primary fissure into the rostral central zone/vermis. This suggests that ACP2 has critical roles in the development of the anterior cerebellum and it may regulate anterior and central zone compartmentation. PMID:24722417

  10. Janus-compartmental alginate microbeads having polydiacetylene liposomes and magnetic nanoparticles for visual lead(II) detection.

    PubMed

    Kang, Do Hyun; Jung, Ho-Sup; Ahn, Namyoung; Yang, Su Min; Seo, Sungbaek; Suh, Kahp-Yang; Chang, Pahn-Shick; Jeon, Noo Li; Kim, Jinsang; Kim, Keesung

    2014-07-01

    Janus-compartmental alginate microbeads having two divided phases of sensory polydiacetylene (PDA) liposomes and magnetic nanoparticles were fabricated for facile sensory applications. The sensory liposomes are composed of PDA for label-free signal generation and 1,2-dipalmitoyl-sn-glycero-3-galloyl (DPGG) lipids whose galloyl headgroup has specific interactions with lead(II). The second phase having magnetic nanoparticles is designed for convenient handling of the microbeads, such as washing, solvent exchange, stirring, and detection, by applying magnetic field. Selective and convenient colorimetric detection of lead(II) and efficient removal of lead(II) by alginate matrix at the same time are demonstrated. PMID:24926923

  11. A Crowdsourced nucleus: Understanding nuclear organization in terms of dynamically networked protein function

    PubMed Central

    Wood, Ashley M.; Garza-Gongora, Arturo G.; Kosak, Steven T.

    2014-01-01

    The spatial organization of the nucleus results in a compartmentalized structure that affects all aspects of nuclear function. This compartmentalization involves genome organization as well as the formation of nuclear bodies and plays a role in many functions, including gene regulation, genome stability, replication, and RNA processing. Here we review the recent findings associated with the spatial organization of the nucleus and reveal that a common theme for nuclear proteins is their ability to participate in a variety of functions and pathways. We consider this multiplicity of function in terms of Crowdsourcing, a recent phenomenon in the world of information technology, and suggest that this model provides a novel way to synthesize the many intersections between nuclear organization and function. PMID:24412853

  12. Measurement of intra-abdominal pressure in large incisional hernia repair to prevent abdominal compartmental syndrome

    PubMed Central

    ANGELICI, A.M.; PEROTTI, B.; DEZZI, C.; AMATUCCI, C.; MANCUSO, G.; CARONNA, R.; PALUMBO, P.

    2016-01-01

    Introduction The repair of large incisional hernias may occasionally lead to a substantial increase in intra-abdominal pressure (IAP), and rarely to abdominal compartmental syndrome (ACS) with subsequent respiratory, vascular, and visceral complications. Measurement of the IAP has recently become a common practice in monitoring critical patients, even though such measurements were obtained in the early 1900s. Patients and Methods A prospective study involving 54 patients undergoing elective abdominal wall gap repair (mean length, 17.4 cm) with a tension-free technique after incisional hernia was conducted. The purpose of the study was to determine whether or not urinary pressure for indirect IAP measurement is a reliable method for the early identification of patients with a higher risk of developing ACS. IAP measurements were performed using a Foley catheter connected to a HOLTECH® medical manometer. IAP values were determined pre-operatively, after anesthetic induction, upon patient awakening, upon patient arrival in the ward after surgery, and 24 h after surgery before removing the catheter. All patients were treated by the same surgical team using a prosthetic composite mesh (PARIETEX®). Results Incisional hernia repair caused an increase in the mean IAP score of 2.68 mmHg in 47 of 54 patients (87.04%); the IAP was decreased in two patients (3.7%) and remained equal in five patients before and 24 h after surgery (9.26%). FEV-1, measured 24 h after surgery, increased in 50 patients (92.6%), remained stable in two patients (3.7%), and decreased in two patients (3.7%). The mean increase in FEV-1 was 0.0676 L (maximum increase = 0.42 L and minimum increase = 0.01 L) in any patient who developed ACS. Conclusions Measurement of urinary bladder pressure has been shown to be easy to perform and free of complications. Measurement of urinary bladder pressure can also be a useful tool to identify patients with a higher risk of developing ACS. PMID:27142823

  13. Structural localization and origin of compartmentalized fluid flow, Comstock lode, Virginia City, Nevada

    USGS Publications Warehouse

    Berger, B.R.; Tingley, J.V.; Drew, L.J.

    2003-01-01

    Bonanza-grade orebodies in epithermal-style mineral deposits characteristically occur as discrete zones within spatially more extensive fault and/or fracture systems. Empirically, the segregation of such systems into compartments of higher and lower permeability appears to be a key process necessary for high-grade ore formation and, most commonly, it is such concentrations of metals that make an epithermal vein district world class. In the world-class silver- and gold-producing Comstock mining district, Nevada, several lines of evidence lead to the conclusion that the Comstock lode is localized in an extensional stepover between right-lateral fault zones. This evidence includes fault geometries, kinematic indicators of slip, the hydraulic connectivity of faults as demonstrated by veins and dikes along faults, and the opening of a normal-fault-bounded, asymmetric basin between two parallel and overlapping northwest-striking, lateral- to lateral-oblique-slip fault zones. During basin opening, thick, generally subeconomic, banded quartz-adularia veins were deposited in the normal fault zone, the Comstock fault, and along one of the bounding lateral fault zones, the Silver City fault. As deformation continued, the intrusion of dikes and small plugs into the hanging wall of the Comstock fault zone may have impeded the ability of the stepover to accommodate displacement on the bounding strike-slip faults through extension within the stepover. A transient period of transpressional deformation of the Comstock fault zone ensued, and the early-stage veins were deformed through boudinaging and hydraulic fragmentation, fault-motion inversion, and high- and low-angle axial rotations of segments of the fault planes and some fault-bounded wedges. This deformation led to the formation of spatially restricted compartments of high vertical permeability and hydraulic connectivity and low lateral hydraulic connectivity. Bonanza orebodies were formed in the compartmentalized zones of

  14. Natural Isotopic Signatures of Variations in Body Nitrogen Fluxes: A Compartmental Model Analysis

    PubMed Central

    Poupin, Nathalie; Mariotti, François; Huneau, Jean-François; Hermier, Dominique; Fouillet, Hélène

    2014-01-01

    Body tissues are generally 15N-enriched over the diet, with a discrimination factor (Δ15N) that varies among tissues and individuals as a function of their nutritional and physiopathological condition. However, both 15N bioaccumulation and intra- and inter-individual Δ15N variations are still poorly understood, so that theoretical models are required to understand their underlying mechanisms. Using experimental Δ15N measurements in rats, we developed a multi-compartmental model that provides the first detailed representation of the complex functioning of the body's Δ15N system, by explicitly linking the sizes and Δ15N values of 21 nitrogen pools to the rates and isotope effects of 49 nitrogen metabolic fluxes. We have shown that (i) besides urea production, several metabolic pathways (e.g., protein synthesis, amino acid intracellular metabolism, urea recycling and intestinal absorption or secretion) are most probably associated with isotope fractionation and together contribute to 15N accumulation in tissues, (ii) the Δ15N of a tissue at steady-state is not affected by variations of its P turnover rate, but can vary according to the relative orientation of tissue free amino acids towards oxidation vs. protein synthesis, (iii) at the whole-body level, Δ15N variations result from variations in the body partitioning of nitrogen fluxes (e.g., urea production, urea recycling and amino acid exchanges), with or without changes in nitrogen balance, (iv) any deviation from the optimal amino acid intake, in terms of both quality and quantity, causes a global rise in tissue Δ15N, and (v) Δ15N variations differ between tissues depending on the metabolic changes involved, which can therefore be identified using simultaneous multi-tissue Δ15N measurements. This work provides proof of concept that Δ15N measurements constitute a new promising tool to investigate how metabolic fluxes are nutritionally or physiopathologically reorganized or altered. The existence of such

  15. The New Jungle. Special Investigation.

    ERIC Educational Resources Information Center

    Hedges, Stephen J.; And Others

    1996-01-01

    By hiring illegal Mexican workers for dangerous jobs, an Iowa meat packing plant keeps wages low and profits high. The host community blames the immigrants for increased crime and has built three new schools to accommodate swelling enrollments of immigrant children with limited English proficiency. The company denies evidence that it knowingly…

  16. Border Safety: Quality Control at the Nuclear Envelope.

    PubMed

    Webster, Brant M; Lusk, C Patrick

    2016-01-01

    The unique biochemical identity of the nuclear envelope confers its capacity to establish a barrier that protects the nuclear compartment and directly contributes to nuclear function. Recent work uncovered quality control mechanisms employing the endosomal sorting complexes required for transport (ESCRT) machinery and a new arm of endoplasmic reticulum-associated protein degradation (ERAD) to counteract the unfolding, damage, or misassembly of nuclear envelope proteins and ensure the integrity of the nuclear envelope membranes. Moreover, cells have the capacity to recognize and triage defective nuclear pore complexes to prevent their inheritance and preserve the longevity of progeny. These mechanisms serve to highlight the diverse strategies used by cells to maintain nuclear compartmentalization; we suggest they mitigate the progression and severity of diseases associated with nuclear envelope malfunction such as the laminopathies. PMID:26437591

  17. Buds from the tree of life: linking compartmentalized prokaryotes and eukaryotes by a non-hyperthermophile common ancestor and implications for understanding Archaean microbial communities

    NASA Astrophysics Data System (ADS)

    Fuerst, John A.; Nisbet, Euan G.

    2004-07-01

    The origin of the first nucleated eukaryote and the nature of the last common ancestor of the three domains of life are major questions in the evolutionary biology of cellular life on Earth, the solutions to which may be linked. Planctomycetes are unusual compartmentalized bacteria that include a membrane-bounded nucleoid. The possibility that they constitute a very deep branch of the domain Bacteria suggests a model for the evolution of the three domains of life from a last common ancestor that was a mesophile or moderate thermophile with a compartmentalized eukaryote-like cell plan. Planctomycetes and some members of the domain Archaea may have retained cell compartmentalization present in an original eukaryote-like last common ancestor of the three domains of life. The implications of this model for possible habitats of the early evolution of domains of cellular life and for interpretation of geological evidence relating to those habitats and the early emergence of life are examined here.

  18. Multi-hollow polymer microspheres with enclosed surfaces and compartmentalized voids prepared by seeded swelling polymerization method.

    PubMed

    Tian, Qiong; Yu, Demei; Zhu, Kaiming; Hu, Guohe; Zhang, Lifeng; Liu, Yuhang

    2016-07-01

    Multi-hollow particles have drawn extensive research interest due to their high specific areas and abundant inner voids, whereas their convenient synthesis still remains challenging. In this paper, we report a simple and convenient method based on seeded swelling polymerization to prepare the multi-hollow microspheres with enclosed surfaces and compartmentalized voids using monodisperse poly (styrene-co-sodium 4-vinylbenzenesulfonate) microspheres as seed particles. A formation mechanism of the multi-hollow structure was proposed involving the processes of water absorption, coalescence and stabilization of water domains, immobilization of multi-hollow structure, and coverage of surface dimples. The influencing parameters on the morphology of the microspheres, including weight ratio of sodium 4-vinylbenzenesulfonate to styrene in the seed particles, dosage of the swelling monomer and the crosslinking agent were systematically investigated. The internal structure of the resultant microspheres could be tuned from solid to multi-hollow by controlling over these parameters. Multi-hollow microspheres with compartmentalized chambers, smooth surfaces and narrow size distributions were obtained as a result. PMID:27046772

  19. 3-D seismic evidence of the effects of carbonate karst collapse on overlying clastic stratigraphy and reservoir compartmentalization

    SciTech Connect

    Hardage, B.A.; Carr, D.L.; Simmons, J.L. Jr.; Jons, R.A.; Lancaster, D.E.; Elphick, R.Y.; Pendleton, V.M.

    1996-09-01

    A multidisciplinary team, composed of stratigraphers, petrophysicists, reservoir engineers, and geophysicists, studied a portion of Boonsville gas field in the Fort Worth Basin of north-central Texas to determine how modern techniques can be combined to understand the mechanisms by which fluvio-deltaic depositional processes create reservoir compartmentalization in a low- to moderate-accommodation basin. An extensive database involving well logs, cores, production, and pressure data from more than 200 wells, 26 mi{sup 2} of 3-D seismic data, vertical seismic profiles, and checkshots was assembled to support this investigation. The authors found the most important geologic influence on stratigraphy and reservoir compartmentalization in this basin to be the existence of numerous karst collapse chimneys over the area covered. These near-vertical karst collapses originated in, or near, the deep Ordovician-age Ellenburger carbonate section and created vertical chimneys extending as high as 2,500 ft above their point of origin, causing significant disruptions in the overlying clastic strata.

  20. TspanC8 tetraspanins differentially regulate the cleavage of ADAM10 substrates, Notch activation and ADAM10 membrane compartmentalization.

    PubMed

    Jouannet, Stéphanie; Saint-Pol, Julien; Fernandez, Laurent; Nguyen, Viet; Charrin, Stéphanie; Boucheix, Claude; Brou, Christel; Milhiet, Pierre-Emmanuel; Rubinstein, Eric

    2016-05-01

    The metalloprotease ADAM10 mediates the shedding of the ectodomain of various cell membrane proteins, including APP, the precursor of the amyloid peptide Aβ, and Notch receptors following ligand binding. ADAM10 associates with the members of an evolutionary conserved subgroup of tetraspanins, referred to as TspanC8, which regulate its exit from the endoplasmic reticulum. Here we show that 4 of these TspanC8 (Tspan5, Tspan14, Tspan15 and Tspan33) which positively regulate ADAM10 surface expression levels differentially impact ADAM10-dependent Notch activation and the cleavage of several ADAM10 substrates, including APP, N-cadherin and CD44. Sucrose gradient fractionation, single molecule tracking and quantitative mass-spectrometry analysis of the repertoire of molecules co-immunoprecipitated with Tspan5, Tspan15 and ADAM10 show that these two tetraspanins differentially regulate ADAM10 membrane compartmentalization. These data represent a unique example where several tetraspanins differentially regulate the function of a common partner protein through a distinct membrane compartmentalization. PMID:26686862

  1. An immunohistochemical study of the compartmentation of metabolism during the development of grape (Vitis vinifera L.) berries.

    PubMed

    Famiani, F; Walker, R P; Técsi, L; Chen, Z H; Proietti, P; Leegood, R C

    2000-04-01

    The compartmentation of key processes in sugar, organic acid and amino acid metabolism was studied during the development of the flesh and seeds of grape (Vitis vinifera L.) berries. Antibodies specific for enzymes involved in sugar (cell wall and vacuolar invertases, pyrophosphate: fructose 6-phosphate phosphotransferase, aldolase, NADP-glyceraldehyde-P dehydrogenase, cytosolic fructose 1,6-bisphosphatase), photosynthesis (Rubisco, fructose 1,6-bisphosphatase, sedoheptulose 1,7-bisphosphatase), amino acid metabolism (cytosolic and mitochondrial aspartate aminotransferases, alanine aminotransferase, glutamate dehydrogenase, glutamine synthetase), organic acid metabolism (phosphoenolpyruvate carboxylase, NAD- and NADP-dependent malic enzyme, ascorbate peroxidase), and lipid metabolism (acetyl CoA carboxylase, isocitrate lyase) were used to determine how their abundance changed during development. There were marked changes in the abundance of many of these enzymes in both the flesh and seeds. The intercellular location of some enzymes was investigated using immunohistochemistry. Several enzymes (e.g. phosphoenolpyruvate carboxylase and those involved in amino acid metabolism) were associated with tissues likely to function in the transport of imported assimilates, such as the vasculature. Although other enzymes (e.g. NADP-malic enzyme and soluble acid invertase, involved in the metabolism of sugars and organic acids) were largely present in the parenchyma cells of the flesh, their distribution was extremely heterogeneous. This study shows that when considering the metabolism of complex structures such as fruit, it is essential to consider how metabolism is compartmentalized between and within different tissues, even when they are apparently structurally homogeneous. PMID:10938859

  2. An empirically adjusted approach to reproductive number estimation for stochastic compartmental models: A case study of two Ebola outbreaks.

    PubMed

    Brown, Grant D; Oleson, Jacob J; Porter, Aaron T

    2016-06-01

    The various thresholding quantities grouped under the "Basic Reproductive Number" umbrella are often confused, but represent distinct approaches to estimating epidemic spread potential, and address different modeling needs. Here, we contrast several common reproduction measures applied to stochastic compartmental models, and introduce a new quantity dubbed the "empirically adjusted reproductive number" with several advantages. These include: more complete use of the underlying compartmental dynamics than common alternatives, use as a potential diagnostic tool to detect the presence and causes of intensity process underfitting, and the ability to provide timely feedback on disease spread. Conceptual connections between traditional reproduction measures and our approach are explored, and the behavior of our method is examined under simulation. Two illustrative examples are developed: First, the single location applications of our method are established using data from the 1995 Ebola outbreak in the Democratic Republic of the Congo and a traditional stochastic SEIR model. Second, a spatial formulation of this technique is explored in the context of the ongoing Ebola outbreak in West Africa with particular emphasis on potential use in model selection, diagnosis, and the resulting applications to estimation and prediction. Both analyses are placed in the context of a newly developed spatial analogue of the traditional SEIR modeling approach. PMID:26574727

  3. Compartmentalization of the precheliceral neuroectoderm in the spider Cupiennius salei: development of the arcuate body, optic ganglia, and mushroom body.

    PubMed

    Doeffinger, Carola; Hartenstein, Volker; Stollewerk, Angelika

    2010-07-01

    Similarly to vertebrates, arthropod brains are compartmentalized into centers with specific neurological functions such as cognition, behavior, and memory. The centers can be further subdivided into smaller functional units. This raises the question of how these compartments are formed during development and how they are integrated into brain centers. We show here for the first time how the precheliceral neuroectoderm of the spider Cupiennius salei is compartmentalized to form the distinct brain centers of the visual system: the optic ganglia, the mushroom bodies, and the arcuate body. The areas of the visual brain centers are defined by the formation of grooves and vesicles and express the proneural gene CsASH1, followed by expression of the neural differentiation marker Prospero. Furthermore, the transcription factor dachshund, which is strongly enriched in the mushroom bodies and the outer optic ganglion of Drosophila, is expressed in the optic anlagen and the mushroom bodies of the spider. The developing brain centers are further subdivided into single neural precursor groups, which become incorporated into the grooves and vesicles but remain distinguishable throughout development, suggesting that they encode spatial information for neural subtype identity. Several molecular and morphological aspects of the development of the optic ganglia and the mushroom bodies are similar in the spider and in insects. Furthermore, we show that the primary engrailed head spot contributes neurons to the optic ganglia of the median eyes, whereas the secondary head spot, which has been associated with the optic ganglia in insects and crustaceans, is absent. PMID:20503430

  4. Computer Modeling of Sand Transport on Mars Using a Compart-Mentalized Fluids Algorithm (CFA)

    NASA Technical Reports Server (NTRS)

    Marshall, J.; Stratton, D.

    1999-01-01

    of sand comminution on Mars. A multiple-grain transport model using just the equations of grain motion describing lift and drag is impossible to develop owing to stochastic effects --the very effects we wish to model. Also, unless we were to employ supercomputing techniques and extremely complex computer codes that could deal with millions of grains simultaneously, it would also be difficult to model grain transport if we attempted to consider every grain in motion. No existing computer models were found that satisfactorily used the equations of motion to arrive at transport flux numbers for the different populations of saltation and reptation. Modeling all the grains in a transport system was an intractable problem within our resources, and thus we developed what we believe to be a new modeling approach to simulating grain transport. The CFA deals with grain populations, but considers them to belong to various compartmentalized fluid units in the boundary layer. In this way, the model circumvents the multigrain problem by dealing primarily with the consequences of grain transport --momentum transfer between air and grains, which is the physical essence of a dynamic grain-fluid mixture. We thus chose to model the aeolian transport process as a superposition of fluids. These fluids include the air as well as particle populations of various properties. The prime property distinguishing these fluids is upward and downward grain motion. In a normal saltation trajectory, a grain's downwind velocity increases with time, so a rising grain will have a smaller downwind velocity than a failing grain. Because of this disparity in rising and falling grain proper-ties, it seemed appropriate to track these as two separate grain populations within the same physical space. The air itself can be considered a separate fluid superimposed within and interacting with the various grain-cloud "fluids". Additional informaiton is contained in the original.

  5. Compartmental modeling of rat macular primary afferents from three-dimensional reconstructions of transmission electron micrographs of serial sections.

    PubMed

    Chimento, T C; Doshay, D G; Ross, M D

    1994-05-01

    1. We cut serial sections through the medial part of the rat vestibular macula for transmission electron microscopic (TEM) examination, computer-assisted three-dimensional (3-D) reconstruction, and compartmental modeling. The ultrastructural research showed that many primary vestibular neurons have an unmyelinated segment, often branched, that extends between the heminode [putative site of the spike initiation zone (SIZ)] and the expanded terminal(s) (calyx, calyces). These segments, termed the neuron branches, and the calyces frequently have spinelike processes of various dimensions that morphologically are afferent, efferent, or reciprocal to other macular neural elements. The purpose of this research was to determine whether morphometric data obtained ultrastructurally were essential to compartmental models [i.e., they influenced action potential (AP) generation, latency, or amplitude] or whether afferent parts could be collapsed into more simple units without markedly affecting results. We used the compartmental modeling program NEURON for this research. 2. In the first set of simulations we studied the relative importance of small variations in process morphology on distant depolarization. A process was placed midway along an isolated piece of a passive neuron branch. The dimensions of the four processes corresponded to actual processes in the serial sections. A synapse, placed on the head of each process, was activated and depolarization was recorded at the end of the neuron branch. When we used 5 nS synaptic conductance, depolarization varied by 3 mV. In a systematic study over a representative range of stem dimensions, depolarization varied by 15.7 mV. Smaller conductances produced smaller effects. Increasing membrane resistivity from 5,000 to 50,000 omega cm2 had no significant effect. 3. In a second series of simulations, using whole primary afferents, we examined the combined effects of process location and afferent morphology on depolarization magnitude

  6. Communication Between the Cell Membrane and the Nucleus: Role of Protein Compartmentalization

    SciTech Connect

    Lelievre, Sophie A; Bissell, Mina J

    1998-10-21

    Understanding how the information is conveyed from outside to inside the cell is a critical challenge for all biologists involved in signal transduction. The flow of information initiated by cell-cell and cell-extracellular matrix contacts is mediated by the formation of adhesion complexes involving multiple proteins. Inside adhesion complexes, connective membrane skeleton (CMS) proteins are signal transducers that bind to adhesion molecules, organize the cytoskeleton, and initiate biochemical cascades. Adhesion complex-mediated signal transduction ultimately directs the formation of supramolecular structures in the cell nucleus, as illustrated by the establishment of multi complexes of DNA-bound transcription factors, and the redistribution of nuclear structural proteins to form nuclear subdomains. Recently, several CMS proteins have been observed to travel to the cell nucleus, suggesting a distinctive role for these proteins in signal transduction. This review focuses on the nuclear translocation of structural signal transducers of the membrane skeleton and also extends our analysis to possible translocation of resident nuclear proteins to the membrane skeleton. This leads us to envision the communication between spatially distant cellular compartments (i.e., membrane skeleton and cell nucleus) as a bidirectional flow of information (a dynamic reciprocity) based on subtle multilevel structural and biochemical equilibria. At one level, it is mediated by the interaction between structural signal transducers and their binding partners, at another level it may be mediated by the balance and integration of signal transducers in different cellular compartments.

  7. Human Immunodeficiency Viruses Appear Compartmentalized to the Female Genital Tract in Cross-Sectional Analyses but Genital Lineages Do Not Persist Over Time

    PubMed Central

    Bull, Marta E.; Heath, Laura M.; McKernan-Mullin, Jennifer L.; Kraft, Kelli M.; Acevedo, Luis; Hitti, Jane E.; Cohn, Susan E.; Tapia, Kenneth A.; Holte, Sarah E.; Dragavon, Joan A.; Coombs, Robert W.; Mullins, James I.; Frenkel, Lisa M.

    2013-01-01

    Background. Whether unique human immunodeficiency type 1 (HIV) genotypes occur in the genital tract is important for vaccine development and management of drug resistant viruses. Multiple cross-sectional studies suggest HIV is compartmentalized within the female genital tract. We hypothesize that bursts of HIV replication and/or proliferation of infected cells captured in cross-sectional analyses drive compartmentalization but over time genital-specific viral lineages do not form; rather viruses mix between genital tract and blood. Methods. Eight women with ongoing HIV replication were studied during a period of 1.5 to 4.5 years. Multiple viral sequences were derived by single-genome amplification of the HIV C2-V5 region of env from genital secretions and blood plasma. Maximum likelihood phylogenies were evaluated for compartmentalization using 4 statistical tests. Results. In cross-sectional analyses compartmentalization of genital from blood viruses was detected in three of eight women by all tests; this was associated with tissue specific clades containing multiple monotypic sequences. In longitudinal analysis, the tissues-specific clades did not persist to form viral lineages. Rather, across women, HIV lineages were comprised of both genital tract and blood sequences. Conclusions. The observation of genital-specific HIV clades only in cross-sectional analysis and an absence of genital-specific lineages in longitudinal analyses suggest a dynamic interchange of HIV variants between the female genital tract and blood. PMID:23315326

  8. Compartmentalized signaling by GPI-anchored ephrin-A5 requires the Fyn tyrosine kinase to regulate cellular adhesion

    PubMed Central

    Davy, Alice; Gale, Nicholas W.; Murray, Elizabeth W.; Klinghoffer, Richard A.; Soriano, Philippe; Feuerstein, Claude; Robbins, Stephen M.

    1999-01-01

    Eph receptor tyrosine kinases and their corresponding surface-bound ligands, the ephrins, provide cues to the migration of cells and growth cones during embryonic development. Here we show that ephrin-A5, which is attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidylinositol-anchor, induces compartmentalized signaling within a caveolae-like membrane microdomain when bound to the extracellular domain of its cognate Eph receptor. The physiological response induced by this signaling event is concomitant with a change in the cellular architecture and adhesion of the ephrin-A5-expressing cells and requires the activity of the Fyn protein tyrosine kinase. This study stresses the relevance of bidirectional signaling involving the ephrins and Eph receptors during brain development. PMID:10601038

  9. Complex-shaped three-dimensional multi-compartmental microparticles generated by diffusional and Marangoni microflows in centrifugally discharged droplets

    PubMed Central

    Hayakawa, Masayuki; Onoe, Hiroaki; Nagai, Ken H.; Takinoue, Masahiro

    2016-01-01

    We report a versatile method for the generation of complex-shaped three-dimensional multi-compartmental (3D-MC) microparticles. Complex-shaped microparticles have recently received much attention for potential application in self-assemblies, micromachines, and biomedical and environmental engineering. Here, we have developed a method based on 3D nonequilibrium-induced microflows (Marangoni and diffusional flows) of microdroplets that are discharged from the tip of a thin capillary in a simple centrifugal microfluidic device. The microparticle shapes can be tuned by the partial dissolution of specific compartments and by the deformation of the precursor microdroplets by manipulating the 3D microflows. We believe that this method will have wide applications in nano- and microscience and technologies. PMID:26861767

  10. Compartmentation of malic acid in mesophyll cells of Kalanchoee daigremontiana: indications of a intracellular cytosolic vesicle transport mechanism

    SciTech Connect

    Balsamo, R.A.; Uribe, E.G.

    1987-04-01

    Leaf tissue was harvested over a 24hr period at one to three hour intervals. The malic acid levels in the tissue were assayed spectrophotometrically and the percent cell volume occupied by cytosolic vesicles in replicate samples was determined. The total volume of the cytosolic vesicles fluctuated throughout the photoperiod concommitantly with malic acid concentrations present in the tissue. An intact leaf tissue section (10.2cm/sup 2/) was radiolabeled with /sup 14/CO/sub 2/ seven hours into the dark period for thirty minutes. Two dimensional thin layer chromatography and electrophoresis of the tissue determined that 96% of the label was incorporated into malic acid. A freeze substitution procedure was initiated followed by microautoradiography (Fisher 1971) which allowed for the tracing of intracellular malic acid migration and compartmentation within the mesophyll cells. The results and interpretation of this experiment will be presented.

  11. A note regarding the mathematical treatment of a class of steady-state compartmental models of the circulation.

    PubMed

    White, Ronald J

    2016-09-01

    A class of steady-state compartmental models of the circulation is examined and it is shown that the mathematical problem for this model class involves a single nonlinear equation. In an important subclass and with certain assumptions regarding the form of the Starling-type cardiac function curves, the single equation is of the form Z = μ + λ log[(1 - Z)/Z] where μ and λ are mathematical parameters related to the physiological parameters of the system and Z is proportional to the cardiac output. This result holds regardless of the number and arrangement of compartments within the model itself or of the number of physiological parameters the model contains. An example of this class with 25 physiological parameters is presented to illustrate this approach. PMID:27587712

  12. The cellular and compartmental profile of mouse retinal glycolysis, tricarboxylic acid cycle, oxidative phosphorylation, and ~P transferring kinases

    PubMed Central

    Rueda, Elda M.; Johnson, Jerry E.; Giddabasappa, Anand; Swaroop, Anand; Brooks, Matthew J.; Sigel, Irena; Chaney, Shawnta Y.

    2016-01-01

    Purpose The homeostatic regulation of cellular ATP is achieved by the coordinated activity of ATP utilization, synthesis, and buffering. Glucose is the major substrate for ATP synthesis through glycolysis and oxidative phosphorylation (OXPHOS), whereas intermediary metabolism through the tricarboxylic acid (TCA) cycle utilizes non-glucose-derived monocarboxylates, amino acids, and alpha ketoacids to support mitochondrial ATP and GTP synthesis. Cellular ATP is buffered by specialized equilibrium-driven high-energy phosphate (~P) transferring kinases. Our goals were twofold: 1) to characterize the gene expression, protein expression, and activity of key synthesizing and regulating enzymes of energy metabolism in the whole mouse retina, retinal compartments, and/or cells and 2) to provide an integrative analysis of the results related to function. Methods mRNA expression data of energy-related genes were extracted from our whole retinal Affymetrix microarray data. Fixed-frozen retinas from adult C57BL/6N mice were used for immunohistochemistry, laser scanning confocal microscopy, and enzymatic histochemistry. The immunoreactivity levels of well-characterized antibodies, for all major retinal cells and their compartments, were obtained using our established semiquantitative confocal and imaging techniques. Quantitative cytochrome oxidase (COX) and lactate dehydrogenase (LDH) activity was determined histochemically. Results The Affymetrix data revealed varied gene expression patterns of the ATP synthesizing and regulating enzymes found in the muscle, liver, and brain. Confocal studies showed differential cellular and compartmental distribution of isozymes involved in glucose, glutamate, glutamine, lactate, and creatine metabolism. The pattern and intensity of the antibodies and of the COX and LDH activity showed the high capacity of photoreceptors for aerobic glycolysis and OXPHOS. Competition assays with pyruvate revealed that LDH-5 was localized in the photoreceptor

  13. Use of a Distributed, Finite-Volume, Hydrologic Model to Assess the Sensitivity of the Everglades to De-compartmentalization

    NASA Astrophysics Data System (ADS)

    Senarath, S. U.

    2002-12-01

    The Everglades, the only remaining subtropical wilderness in the continental USA, is the home to a number of threatened and endangered species. Although the pre-drainage Everglades covered an area of approximately 11,048 km2, urbanization and farming have reduced its area by approximately 50%. The remaining Everglades has also changed as a result of drainage and compartmentalization by over 2,200 km of levees and canals. This area is also adversely affected by exotic species, nutrient enrichment, contaminants and altered freshwater flows. The \\8 billion Comprehensive Everglades Restoration Plan provides a ``framework and guide to restore, protect, and preserve the water resources of central and southern Florida, including the Everglades.'' The success of this project, one of the largest eco-system restoration projects in the world, depends heavily on our understanding of the quantity, quality, timing and distribution of South Florida's pre-drainage freshwater flow. Consequently, accurate hydrologic modeling is crucial for the restoration of the greater Everglades ecosystem. The Regional Simulation Model (RSM) developed by the South Florida Water Management District is currently being used to investigate the effect of de-compartmentalization on freshwater flow dynamics in parts of the remaining Everglades which includes the Everglades National Park and the Big Cypress National Preserve. The RSM is an implicit, finite-volume, continuous, distributed, integrated surface/ground-water model, capable of simulating one-dimensional canal flow and two-dimensional overland flow in arbitrarily shaped areas using a variable triangular mesh. It has physically-based formulations for the simulation of overland and groundwater flow, evapo-transpiration, infiltration, levee seepage, and canal and structure flows. It is capable of simulating features that are unique to South Florida such as low-relief topography, high water tables, saturation-excess runoff, depth

  14. Complex-shaped three-dimensional multi-compartmental microparticles generated by diffusional and Marangoni microflows in centrifugally discharged droplets

    NASA Astrophysics Data System (ADS)

    Hayakawa, Masayuki; Onoe, Hiroaki; Nagai, Ken H.; Takinoue, Masahiro

    2016-02-01

    We report a versatile method for the generation of complex-shaped three-dimensional multi-compartmental (3D-MC) microparticles. Complex-shaped microparticles have recently received much attention for potential application in self-assemblies, micromachines, and biomedical and environmental engineering. Here, we have developed a method based on 3D nonequilibrium-induced microflows (Marangoni and diffusional flows) of microdroplets that are discharged from the tip of a thin capillary in a simple centrifugal microfluidic device. The microparticle shapes can be tuned by the partial dissolution of specific compartments and by the deformation of the precursor microdroplets by manipulating the 3D microflows. We believe that this method will have wide applications in nano- and microscience and technologies.

  15. Effect of compartmentalization of donor and acceptor on the ultrafast resonance energy transfer from DAPI to silver nanoclusters

    NASA Astrophysics Data System (ADS)

    Prajapati, Roopali; Chatterjee, Surajit; Kannaujiya, Krishna K.; Mukherjee, Tushar Kanti

    2016-06-01

    The mechanism and dynamics of excitation energy transfer (EET) from photo-excited 4',6-diamidino-2-phenylindole (DAPI) to silver nanoclusters (Ag NCs) and its subsequent modulation in the presence of cationic polymer poly(diallyldimethylammonium chloride) (PDADMAC) and Calf Thymus DNA (CT-DNA) have been demonstrated using steady-state fluorescence and femtosecond fluorescence upconversion techniques. The synthesized Ag NCs were characterized using FTIR, mass spectrometry, XPS, HRTEM, DLS, UV-Vis and PL spectroscopy. Mass spectrometric analysis reveals the formation of ultrasmall Ag4 NCs with a small amount of Ag5 NCs. UV-Vis and PL spectra reveal distinct molecular-like optoelectronic behaviour of these ultrasmall Ag NCs. The dihydrolipoic acid-capped Ag NCs strongly quench the fluorescence of DAPI with concomitant increase in its photoluminescence (PL) intensity at 675 nm. This steady-state fluorescence quenching proceeds with a significant shortening of the fluorescence lifetime of DAPI in the presence of Ag NCs, signifying the nonradiative Förster resonance energy transfer (FRET) from DAPI to Ag NCs. Various energy transfer parameters have been estimated from FRET theory. The present FRET pair shows a characteristic Förster distance of 2.45 nm and can be utilized as a reporter of short-range distances in various FRET based applications. Moreover, this nonradiative FRET is completely suppressed in the presence of both 0.2 wt% PDADMAC and CT-DNA. Our results reveal selective compartmentalization of Ag NCs and DAPI in the presence of 0.2 wt% PDADMAC and CT-DNA, respectively. This selective compartmentalization of donor and acceptor and the subsequent modification of the FRET process may find application in various sensing, photovoltaic, and light harvesting applications.The mechanism and dynamics of excitation energy transfer (EET) from photo-excited 4',6-diamidino-2-phenylindole (DAPI) to silver nanoclusters (Ag NCs) and its subsequent modulation in the presence

  16. Molecular analysis reveals high compartmentalization in aphid-primary parasitoid networks and low parasitoid sharing between crop and noncrop habitats.

    PubMed

    Derocles, Stephane A P; Le Ralec, Anne; Besson, Mathilde M; Maret, Marion; Walton, Alan; Evans, Darren M; Plantegenest, Manuel

    2014-08-01

    The ecosystem service of insect pest regulation by natural enemies, such as primary parasitoids, may be enhanced by the presence of uncultivated, semi-natural habitats within agro-ecosystems, although quantifying such host-parasitoid interactions is difficult. Here, we use rRNA 16S gene sequencing to assess both the level of parasitism by Aphidiinae primary parasitoids and parasitoid identity on a large sample of aphids collected in cultivated and uncultivated agricultural habitats in Western France. We used these data to construct ecological networks to assess the level of compartmentalization between aphid and parasitoid food webs of cultivated and uncultivated habitats. We evaluated the extent to which uncultivated margins provided a resource for parasitoids shared between pest and nonpest aphids. We compared the observed quantitative ecological network described by our molecular approach to an empirical qualitative network based on aphid-parasitoid interactions from traditional rearing data found in the literature. We found that the molecular network was highly compartmentalized and that parasitoid sharing is relatively rare between aphids, especially between crop and noncrop compartments. Moreover, the few cases of putative shared generalist parasitoids were questionable and could be due to the lack of discrimination of cryptic species or from intraspecific host specialization. Our results suggest that apparent competition mediated by Aphidiinae parasitoids is probably rare in agricultural areas and that the contribution of field margins as a source of these biocontrol agents is much more limited than expected. Further large-scale (spatial and temporal) studies on other crops and noncrop habitats are needed to confirm this. PMID:24612360

  17. Effect of compartmentalization of donor and acceptor on the ultrafast resonance energy transfer from DAPI to silver nanoclusters.

    PubMed

    Prajapati, Roopali; Chatterjee, Surajit; Kannaujiya, Krishna K; Mukherjee, Tushar Kanti

    2016-07-14

    The mechanism and dynamics of excitation energy transfer (EET) from photo-excited 4',6-diamidino-2-phenylindole (DAPI) to silver nanoclusters (Ag NCs) and its subsequent modulation in the presence of cationic polymer poly(diallyldimethylammonium chloride) (PDADMAC) and Calf Thymus DNA (CT-DNA) have been demonstrated using steady-state fluorescence and femtosecond fluorescence upconversion techniques. The synthesized Ag NCs were characterized using FTIR, mass spectrometry, XPS, HRTEM, DLS, UV-Vis and PL spectroscopy. Mass spectrometric analysis reveals the formation of ultrasmall Ag4 NCs with a small amount of Ag5 NCs. UV-Vis and PL spectra reveal distinct molecular-like optoelectronic behaviour of these ultrasmall Ag NCs. The dihydrolipoic acid-capped Ag NCs strongly quench the fluorescence of DAPI with concomitant increase in its photoluminescence (PL) intensity at 675 nm. This steady-state fluorescence quenching proceeds with a significant shortening of the fluorescence lifetime of DAPI in the presence of Ag NCs, signifying the nonradiative Förster resonance energy transfer (FRET) from DAPI to Ag NCs. Various energy transfer parameters have been estimated from FRET theory. The present FRET pair shows a characteristic Förster distance of 2.45 nm and can be utilized as a reporter of short-range distances in various FRET based applications. Moreover, this nonradiative FRET is completely suppressed in the presence of both 0.2 wt% PDADMAC and CT-DNA. Our results reveal selective compartmentalization of Ag NCs and DAPI in the presence of 0.2 wt% PDADMAC and CT-DNA, respectively. This selective compartmentalization of donor and acceptor and the subsequent modification of the FRET process may find application in various sensing, photovoltaic, and light harvesting applications. PMID:27304093

  18. Compartmentalized expression of light-induced clock genes in the suprachiasmatic nucleus of the diurnal grass rat (Arvicanthis niloticus)

    PubMed Central

    Ramanathan, Chidambaram; Campbell, Amy; Tomczak, Ashley; Nunez, Antonio A.; Smale, Laura; Yan, Lily

    2009-01-01

    Photic responses of the circadian system are mediated through light-induced clock gene expression in the suprachiasmatic nucleus (SCN). In nocturnal rodents, depending on the timing of light exposure, Per1 and Per2 gene expression shows distinct compartmentalized patterns that correspond to the behavioral responses. Whether the gene-and region-specific induction patterns are unique to nocturnal animals, or are also present in diurnal species is unknown. We explored this question by examining the light-induced Per1 and Per2 gene expression in functionally distinct SCN sub regions, using diurnal grass rats Arvicanthis niloticus. Light exposure during nighttime induced Per1 and Per2 expression in the SCN, showing unique spatiotemporal profiles depending on the phase of the light exposure. After a phase delaying light pulse (LP) in the early night, strong Per1 induction was observed in the retinorecipient core region of the SCN, while strong Per2 induction was observed throughout the entire SCN. After a phase advancing LP in the late night, Per1 was first induced in the core and then extended into the whole SCN, accompanied by a weak Per2 induction. This compartmentalized expression pattern is very similar to that observed in nocturnal rodents, suggesting that the same molecular and intercellular pathways underlying acute photic responses are present in both diurnal and nocturnal species. However, after a LP in early subjective day, which induces phase advances in diurnal grass rats, but not in nocturnal rodents, we did not observe any Per1 or Per2 induction in the SCN. This result suggests that in spite of remarkable similarities in the SCN of diurnal and nocturnal rodents, unique mechanisms are involved in mediating the phase shifts of diurnal animals during the subjective day. PMID:19393297

  19. Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport.

    PubMed Central

    Rebouche, C J; Engel, A G

    1984-01-01

    The human primary carnitine deficiency syndromes are potentially fatal disorders affecting children and adults. The molecular etiologies of these syndromes have not been determined. In this investigation, we considered the hypothesis that these syndromes result from defective transport of carnitine into tissues, particularly skeletal muscle. The problem was approached by mathematical modeling, by using the technique of kinetic compartmental analysis. A tracer dose of L-[methyl-3H]carnitine was administered intravenously to six normal subjects, one patient with primary muscle carnitine deficiency (MCD), and four patients with primary systemic carnitine deficiency (SCD). Specific radioactivity was followed in plasma for 28 d. A three-compartment model (extracellular fluid, muscle, and "other tissues") was adopted. Rate constants, fluxes, pool sizes, and turnover times were calculated. Results of these calculations indicated reduced transport of carnitine into muscle in both forms of primary carnitine deficiency. However, in SCD, the reduced rate of carnitine transport was attributed to reduced plasma carnitine concentration. In MCD, the results are consistent with an intrinsic defect in the transport process. Abnormal fluctuations of the plasma carnitine, but of a different form, occurred in MCD and SCD. The significance of these are unclear, but in SCD they suggest abnormal regulation of the muscle/plasma carnitine concentration gradient. In 8 of 11 subjects, carnitine excretion was less than dietary carnitine intake. Carnitine excretion rates calculated by kinetic compartmental analysis were higher than corresponding rates measured directly, indicating degradation of carnitine. However, we found no radioactive metabolites of L-[methyl-3H]carnitine in urine. These observations suggest that dietary carnitine was metabolized in the gastrointestinal tract. PMID:6707204

  20. Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs

    PubMed Central

    Li, Jane; Smith, Corey; Edwards, Jarem; Sierro, Frederic; Feng, Carl G.; Khanna, Rajiv; Bell, Andrew; Hislop, Andrew D.; Tangye, Stuart G.; Rickinson, Alan B.; Gebhardt, Thomas; Britton, Warwick J.

    2016-01-01

    Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103—, and were retained within the spleen and tonsils in the absence of recent T cell stimulation. These two types of memory cells were distinct not only in their phenotype and transcriptional profile, but also in their anatomical localization within tonsils and spleen. The EBV-specific, but not CMV-specific, CD8+ memory T cells preferentially accumulated in the tonsils and acquired a phenotype that ensured their retention at the epithelial sites where EBV replicates. In vitro studies revealed that the cytokine IL-15 can potentiate the retention of circulating effector memory CD8+ T cells by down-regulating the expression of sphingosine-1-phosphate receptor, required for T cell exit from tissues, and its transcriptional activator, Kruppel-like factor 2 (KLF2). Within the tonsils the expression of IL-15 was detected in regions where CD8+ T cells localized, further supporting a role for this cytokine in T cell retention. Together this study provides evidence for the compartmentalization of distinct types of resident memory T cells that could contribute to the long-term protection against persisting viral infections. PMID:27540722

  1. Lipid Droplet-Associated Proteins (LDAPs) Are Required for the Dynamic Regulation of Neutral Lipid Compartmentation in Plant Cells.

    PubMed

    Gidda, Satinder K; Park, Sunjung; Pyc, Michal; Yurchenko, Olga; Cai, Yingqi; Wu, Peng; Andrews, David W; Chapman, Kent D; Dyer, John M; Mullen, Robert T

    2016-04-01

    Eukaryotic cells compartmentalize neutral lipids into organelles called lipid droplets (LDs), and while much is known about the role of LDs in storing triacylglycerols in seeds, their biogenesis and function in nonseed tissues are poorly understood. Recently, we identified a class of plant-specific, lipid droplet-associated proteins (LDAPs) that are abundant components of LDs in nonseed cell types. Here, we characterized the three LDAPs in Arabidopsis (Arabidopsis thaliana) to gain insight to their targeting, assembly, and influence on LD function and dynamics. While all three LDAPs targeted specifically to the LD surface, truncation analysis of LDAP3 revealed that essentially the entire protein was required for LD localization. The association of LDAP3 with LDs was detergent sensitive, but the protein bound with similar affinity to synthetic liposomes of various phospholipid compositions, suggesting that other factors contributed to targeting specificity. Investigation of LD dynamics in leaves revealed that LD abundance was modulated during the diurnal cycle, and characterization of LDAP misexpression mutants indicated that all three LDAPs were important for this process. LD abundance was increased significantly during abiotic stress, and characterization of mutant lines revealed that LDAP1 and LDAP3 were required for the proper induction of LDs during heat and cold temperature stress, respectively. Furthermore, LDAP1 was required for proper neutral lipid compartmentalization and triacylglycerol degradation during postgerminative growth. Taken together, these studies reveal that LDAPs are required for the maintenance and regulation of LDs in plant cells and perform nonredundant functions in various physiological contexts, including stress response and postgerminative growth. PMID:26896396

  2. Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs.

    PubMed

    Woon, Heng Giap; Braun, Asolina; Li, Jane; Smith, Corey; Edwards, Jarem; Sierro, Frederic; Feng, Carl G; Khanna, Rajiv; Elliot, Michael; Bell, Andrew; Hislop, Andrew D; Tangye, Stuart G; Rickinson, Alan B; Gebhardt, Thomas; Britton, Warwick J; Palendira, Umaimainthan

    2016-08-01

    Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103-, and were retained within the spleen and tonsils in the absence of recent T cell stimulation. These two types of memory cells were distinct not only in their phenotype and transcriptional profile, but also in their anatomical localization within tonsils and spleen. The EBV-specific, but not CMV-specific, CD8+ memory T cells preferentially accumulated in the tonsils and acquired a phenotype that ensured their retention at the epithelial sites where EBV replicates. In vitro studies revealed that the cytokine IL-15 can potentiate the retention of circulating effector memory CD8+ T cells by down-regulating the expression of sphingosine-1-phosphate receptor, required for T cell exit from tissues, and its transcriptional activator, Kruppel-like factor 2 (KLF2). Within the tonsils the expression of IL-15 was detected in regions where CD8+ T cells localized, further supporting a role for this cytokine in T cell retention. Together this study provides evidence for the compartmentalization of distinct types of resident memory T cells that could contribute to the long-term protection against persisting viral infections. PMID:27540722

  3. A compartmental model of uranium in human hair for protracted ingestion of natural uranium in drinking water.

    PubMed

    Li, W B; Karpas, Z; Salonen, L; Kurttio, P; Muikku, M; Wahl, W; Höllriegl, V; Hoeschen, C; Oeh, U

    2009-06-01

    To predict uranium in human hair due to chronic exposure through drinking water, a compartment representing human hair was added into the uranium biokinetic model developed by the International Commission on Radiological Protection (ICRP). The hair compartmental model was used to predict uranium excretion in human hair as a bioassay indicator due to elevated uranium intakes. Two excretion pathways, one starting from the compartment of plasma and the other from the compartment of intermediate turnover soft tissue, are assumed to transfer uranium to the compartment of hair. The transfer rate was determined from reported uranium contents in urine and in hair, taking into account the hair growth rate of 0.1 g d(-1). The fractional absorption in the gastrointestinal tract of 0.6% was found to fit best to describe the measured uranium levels among the users of drilled wells in Finland. The ingestion dose coefficient for (238)U, which includes its progeny of (234)Th, (234m)Pa, and (234)Pa, was calculated equal to 1.3 x 10(-8) Sv Bq(-1) according to the hair compartmental model. This estimate is smaller than the value of 4.5 x 10(-8) Sv Bq(-1) published by ICRP for the members of the public. In this new model, excretion of uranium through urine is better represented when excretion to the hair compartment is accounted for and hair analysis can provide a means for assessing the internal body burden of uranium. The model is applicable for chronic exposure as well as for an acute exposure incident. In the latter case, the hair sample can be collected and analyzed even several days after the incident, whereas urinalysis requires sample collection shortly after the exposure. The model developed in this study applies to ingestion intakes of uranium. PMID:19430216

  4. Compartmental flux and in situ methods underestimate total feed nitrogen as judged by the omasal sampling method due to ignoring soluble feed nitrogen flow.

    PubMed

    Huhtanen, Pekka; Bayat, Alireza; Krizsan, Sophie J; Vanhatalo, Aila

    2014-02-01

    The objective of the present study was to estimate ruminal feed N outflow in lactating cows using the omasal sampling, compartmental flux or in situ method. A total of five ruminally fistulated Finnish Ayrshire dairy cows were used in a 5 × 5 Latin square study with 21 d periods. Experimental silages of grass or red clover harvested at two stages of maturity in addition to a supplement of 9·0 kg concentrate/d were fed to the cows. In vivo omasal N flow was determined using the omasal sampling technique. Ruminal in situ N flow was calculated from N intake and degradability (38 μm nylon bags). The samples of ruminal contents and faeces were divided into seven particle-size fractions by wet sieving; the concentrations of indigestible neutral-detergent fibre and N were used to calculate N flow in the compartmental flux method. In vivo omasal N flow was greater for the red clover silage diets than for the grass silage diets. The N flow calculated using the compartmental flux technique and that calculated using the in situ technique were highly correlated, but both were less than and poorly correlated with the in vivo N flow. In both in situ and compartmental flux techniques, forage maturity increased the particle-associated N flow, with the increase being significantly greater for the red clover diets than for the grass silage diets. In conclusion, the compartmental flux and in situ methods described the N flow associated with the particle fractions rather than the total ruminal outflow of feed N. PMID:23962678

  5. Experimental infection of highly and low pathogenic avian influenza viruses to chickens, ducks, tree sparrows, jungle crows, and black rats for the evaluation of their roles in virus transmission.

    PubMed

    Hiono, Takahiro; Okamatsu, Masatoshi; Yamamoto, Naoki; Ogasawara, Kohei; Endo, Mayumi; Kuribayashi, Saya; Shichinohe, Shintaro; Motohashi, Yurie; Chu, Duc-Huy; Suzuki, Mizuho; Ichikawa, Takaya; Nishi, Tatsuya; Abe, Yuri; Matsuno, Keita; Tanaka, Kazuyuki; Tanigawa, Tsutomu; Kida, Hiroshi; Sakoda, Yoshihiro

    2016-01-15

    Highly pathogenic avian influenza viruses (HPAIVs) have spread in both poultry and wild birds. Determining transmission routes of these viruses during an outbreak is essential for the control of avian influenza. It has been widely postulated that migratory ducks play crucial roles in the widespread dissemination of HPAIVs in poultry by carrying viruses along with their migrations; however close contacts between wild migratory ducks and poultry are less likely in modern industrial poultry farming settings. Therefore, we conducted experimental infections of HPAIVs and low pathogenic avian influenza viruses (LPAIVs) to chickens, domestic ducks, tree sparrows, jungle crows, and black rats to evaluate their roles in virus transmission. The results showed that chickens, ducks, sparrows, and crows were highly susceptible to HPAIV infection. Significant titers of virus were recovered from the sparrows and crows infected with HPAIVs, which suggests that they potentially play roles of transmission of HPAIVs to poultry. In contrast, the growth of LPAIVs was limited in each of the animals tested compared with that of HPAIVs. The present results indicate that these common synanthropes play some roles in influenza virus transmission from wild birds to poultry. PMID:26711036

  6. Nuclear structure, gene expression and development.

    PubMed

    Brown, K

    1999-01-01

    This article considers the extent to which features of nuclear structure are involved in the regulation of genome function. The recent renaissance in imaging technology has inspired a new determination to assign specific functions to nuclear domains or structures, many of which have been described as "factories" to express the idea that they coordinate nuclear processes in an efficient way. Visual data have been combined with genetic and biochemical information to support the idea that nuclear organization has functional significance. Particular DNA sequences or chromatin structures may nucleate domains that are permissive or restrictive of transcription, to which active or inactive loci could be recruited. Associations within the nucleus, as well as many nuclear structures, are transient and change dynamically during cell cycle progression and development. Despite this complexity, elucidation of the possible structural basis of epigenetic phenomena, such as the inheritance of a "cellular memory" of gene expression status, is an important goal for cell biology. Topics for discussion include the regulatory effect of chromatin structure on gene expression, putative "nuclear addresses" for genes and proteins, the functional significance of nuclear bodies, and the role of the nuclear matrix in nuclear compartmentalization. PMID:10651237

  7. Compartmentalized microchannel array for high-throughput analysis of single cell polarized growth and dynamics

    PubMed Central

    Geng, Tao; Bredeweg, Erin L.; Szymanski, Craig J.; Liu, Bingwen; Baker, Scott E.; Orr, Galya; Evans, James E.; Kelly, Ryan T.

    2015-01-01

    Interrogating polarized growth is technologically challenging due to extensive cellular branching and uncontrollable environmental conditions in conventional assays. Here we present a robust and high-performance microfluidic system that enables observations of polarized growth with enhanced temporal and spatial control over prolonged periods. The system has built-in tunability and versatility to accommodate a variety of scientific applications requiring precisely controlled environments. Using the model filamentous fungus, Neurospora crassa, our microfluidic system enabled direct visualization and analysis of cellular heterogeneity in a clonal fungal cell population, nuclear distribution and dynamics at the subhyphal level, and quantitative dynamics of gene expression with single hyphal compartment resolution in response to carbon source starvation and exchange. Although the microfluidic device is demonstrated on filamentous fungi, the technology is immediately extensible to a wide array of other biosystems that exhibit similar polarized cell growth, with applications ranging from bioenergy production to human health. PMID:26530004

  8. Compartmentalized microchannel array for high-throughput analysis of single cell polarized growth and dynamics

    SciTech Connect

    Geng, Tao; Bredeweg, Erin L.; Szymanski, Craig J.; Liu, Bingwen; Baker, Scott E.; Orr, Galya; Evans, James E.; Kelly, Ryan T.

    2015-11-04

    Here, interrogating polarized growth is technologically challenging due to extensive cellular branching and uncontrollable environmental conditions in conventional assays. Here we present a robust and high-performance microfluidic system that enables observations of polarized growth with enhanced temporal and spatial control over prolonged periods. The system has built-in tunability and versatility to accommodate a variety of science applications requiring precisely controlled environments. Using the model filamentous fungus, Neurospora crassa, this microfluidic system enabled direct visualization and analysis of cellular heterogeneity in a clonal fungal cell population, nuclear distribution and dynamics at the subhyphal level, and quantitative dynamics of gene expression with single hyphal compartment resolution in response to carbon source starvation and exchange experiments. Although the microfluidic device is demonstrated on filamentous fungi, our technology is immediately extensible to a wide array of other biosystems that exhibit similar polarized cell growth with applications ranging from bioenergy production to human health.

  9. Compartmentalized microchannel array for high-throughput analysis of single cell polarized growth and dynamics

    DOE PAGESBeta

    Geng, Tao; Bredeweg, Erin L.; Szymanski, Craig J.; Liu, Bingwen; Baker, Scott E.; Orr, Galya; Evans, James E.; Kelly, Ryan T.

    2015-11-04

    Here, interrogating polarized growth is technologically challenging due to extensive cellular branching and uncontrollable environmental conditions in conventional assays. Here we present a robust and high-performance microfluidic system that enables observations of polarized growth with enhanced temporal and spatial control over prolonged periods. The system has built-in tunability and versatility to accommodate a variety of science applications requiring precisely controlled environments. Using the model filamentous fungus, Neurospora crassa, this microfluidic system enabled direct visualization and analysis of cellular heterogeneity in a clonal fungal cell population, nuclear distribution and dynamics at the subhyphal level, and quantitative dynamics of gene expression withmore » single hyphal compartment resolution in response to carbon source starvation and exchange experiments. Although the microfluidic device is demonstrated on filamentous fungi, our technology is immediately extensible to a wide array of other biosystems that exhibit similar polarized cell growth with applications ranging from bioenergy production to human health.« less

  10. Role of cyclic nucleotide phosphodiesterase isoforms in cAMP compartmentation following β2-adrenergic stimulation of ICa,L in frog ventricular myocytes

    PubMed Central

    Jurevičius, Jonas; Skeberdis, V Arvydas; Fischmeister, Rodolphe

    2003-01-01

    The role of cyclic nucleotide phosphodiesterase (PDE) isoforms in the β2-adrenergic stimulation of the L-type Ca2+ current (ICa,L) was investigated in frog ventricular myocytes using double patch-clamp and double-barrelled microperfusion techniques. Isoprenaline (ISO, 1 nM to 10 μM) was applied on one half of the cell, either alone or in the presence of PDE inhibitors, and the local and distant responses of ICa,L were used to determine the gradient of local vs. distant cAMP concentration (α). IBMX (100 μM), a non-selective PDE inhibitor, reduced α from 40 to 4.4 indicating a 9-fold reduction in intracellular cAMP compartmentation when all PDE activity was blocked. While PDE1 and PDE2 inhibition had no effect, PDE3 inhibition by milrinone (3 μM) or PDE4 inhibition by Ro 20-1724 (3 μM) reduced α by 6- and 4-fold, respectively. A simultaneous application of milrinone and Ro 20-1724 produced a similar effect to IBMX, showing that PDE3 and PDE4 were the major PDEs accounting for cAMP compartmentation. Okadaic acid (3 μM), a non-selective phosphatase inhibitor, or H89 (1 μM), an inhibitor of cAMP-dependent protein kinase (PKA), had no effect on the distant response of ICa,L to ISO indicating that PDE activation by PKA played a minor role in cAMP compartmentation. Our results demonstrate that PDE activity determines the degree of cAMP compartmentation in frog ventricular cells upon β2-adrenergic stimulation. PDE3 and PDE4 subtypes play a major role in this process, and contribute equally to ensure a functional coupling of β2-adrenergic receptors with nearby Ca2+ channels via local elevations of cAMP. PMID:12815180

  11. Acute effects of different inspiratory efforts on ventilatory pattern and chest wall compartmental distribution in elderly women.

    PubMed

    Muniz de Souza, Helga; Rocha, Taciano; Campos, Shirley Lima; Brandão, Daniella Cunha; Fink, James B; Aliverti, Andrea; de Andrade, Armele Dornelas

    2016-06-15

    It is not completely described how aging affect ventilatory kinematics and what are the mechanisms adopted by the elderly population to overcome these structural modifications. Given this, the aim was to evaluate the acute effects of different inspiratory efforts on ventilatory pattern and chest wall compartmental distribution in elderly women. Variables assessed included: tidal volume (Vt), total chest wall volume (Vcw), pulmonary rib cage (Vrcp%), abdominal rib cage (Vrca%) and abdominal compartment (Vab%) relative contributions to tidal volume. These variables were assessed during quiet breathing, maximal inspiratory pressure maneuver (MIP), and moderate inspiratory resistance (MIR; i.e., 40% of MIP). 22 young women (age: 23.9±2.5 years) and 22 elderly women (age: 68.2±5.0 years) participated to this study. It was possible to show that during quiet breathing, Vab% was predominant in elderly (p<0.001), in young, however, Vab% was similar to Vrcp% (p=0.095). During MIR, Vrcp% was predominant in young (p<0.001) and comparable to Vab% in elderly (p=0.249). When MIP was imposed, both groups presented a predominance of Vrcp%. In conclusion, there are differences in abdominal kinematics between young and elderly women during different inspiratory efforts. In elderly, during moderate inspiratory resistance, the pattern is beneficial, deep, and slow. Although, during maximal inspiratory resistance, the ventilatory pattern seems to predict imminent muscle fatigue. PMID:26900004

  12. Spatial Phosphoprotein Profiling Reveals a Compartmentalized Extracellular Signal-regulated Kinase Switch Governing Neurite Growth and Retraction

    SciTech Connect

    Wang, Yingchun; Yang, Feng; Fu, Yi; Huang, Xiahe; Wang, Wei; Jiang, Xining; Gritsenko, Marina A.; Zhao, Rui; Monroe, Matthew E.; Pertz, Olivier C.; Purvine, Samuel O.; Orton, Daniel J.; Jacobs, Jon M.; Camp, David G.; Smith, Richard D.; Klemke, Richard L.

    2011-05-20

    Abstract - Brain development and spinal cord regeneration require neurite sprouting and growth cone navigation in response to extension and collapsing factors present in the extracellular environment. These external guidance cues control neurite growth cone extension and retraction processes through intracellular protein phosphorylation of numerous cytoskeletal, adhesion, and polarity complex signaling proteins. However, the complex kinase/substrate signaling networks that mediate neuritogenesis have not been investigated. Here, we compare the neurite phosphoproteome under growth and retraction conditions using neurite purification methodology combined with mass spectrometry. More than 4000 non-redundant phosphorylation sites from 1883 proteins have been annotated and mapped to signaling pathways that control kinase/phosphatase networks, cytoskeleton remodeling, and axon/dendrite specification. Comprehensive informatics and functional studies revealed a compartmentalized ERK activation/deactivation cytoskeletal switch that governs neurite growth and retraction, respectively. Our findings provide the first system-wide analysis of the phosphoprotein signaling networks that enable neurite growth and retraction and reveal an important molecular switch that governs neuritogenesis.

  13. Drug compartmentalization as strategy to improve the physico-chemical properties of diclofenac sodium loaded niosomes for topical applications.

    PubMed

    Tavano, Lorena; de Cindio, Bruno; Picci, Nevio; Ioele, Giuseppina; Muzzalupo, Rita

    2014-12-01

    The objective of this research was to study the effect of diclofenac sodium compartmentalization on the physico-chemical properties (such as size, drug entrapment efficiency and percutaneous permeation across rabbit skin) of niosomal vesicles used as carriers. Niosomes were prepared starting from nonionic commercial surfactants belonging to the class of Polysorbates and Pluronics: mixtures of Span 60/F127 and Tween 60/F127 at different ratios were used to obtain vesicles and all formulations were compared in terms of dimensions, morphology, polydispersity index and entrapment efficiency. Moreover, the enhancing effect of niosomes on the ex vivo percutaneous penetration of diclofenac sodium was investigated using Franz-type diffusion chambers and compared to that obtained by using the corresponding drug solution. Results demonstrated that niosomes were spherical and homogeneous in shape. Their size was found to be dependent on the hydrophile-lipophile balance of the surfactant mixture: increasing hydrophobicity resulted in smaller vesicles. Drug incorporation led to a significant variation in vesicle size dependently from the compartment in which the drug was located. The permeation of diclofenac from free solution used as control was found to be lower respect to that obtained for all niosomal formulations, that can be considered as percutaneous permeation enhancers. In particular, the results indicated that the highest cumulative amounts of diclofenac permeated across rabbit skin after 24 h were obtained by formulations in which the drug was located in the aqueous core. PMID:25129111

  14. Long-term results of compartmental arthroplasties of the knee: Long term results of partial knee arthroplasty.

    PubMed

    Parratte, S; Ollivier, M; Lunebourg, A; Abdel, M P; Argenson, J-N

    2015-10-01

    Partial knee arthroplasty (PKA), either medial or lateral unicompartmental knee artroplasty (UKA) or patellofemoral arthroplasty (PFA) are a good option in suitable patients and have the advantages of reduced operative trauma, preservation of both cruciate ligaments and bone stock, and restoration of normal kinematics within the knee joint. However, questions remain concerning long-term survival. The goal of this review article was to present the long-term results of medial and lateral UKA, PFA and combined compartmental arthroplasty for multicompartmental disease. Medium- and long-term studies suggest reasonable outcomes at ten years with survival greater than 95% in UKA performed for medial osteoarthritis or osteonecrosis, and similarly for lateral UKA, particularly when fixed-bearing implants are used. Disappointing long-term outcomes have been observed with the first generation of patellofemoral implants, as well as early Bi-Uni (i.e., combined medial and lateral UKA) or Bicompartmental (combined UKA and PFA) implants due to design and fixation issues. Promising short- and med-term results with the newer generations of PFAs and bicompartmental arthroplasties will require long-term confirmation. PMID:26430081

  15. Compartmentalized energy transfer in cardiomyocytes: use of mathematical modeling for analysis of in vivo regulation of respiration.

    PubMed Central

    Aliev, M K; Saks, V A

    1997-01-01

    The mathematical model of the compartmentalized energy transfer system in cardiac myocytes presented includes mitochondrial synthesis of ATP by ATP synthase, phosphocreatine production in the coupled mitochondrial creatine kinase reaction, the myofibrillar and cytoplasmic creatine kinase reactions, ATP utilization by actomyosin ATPase during the contraction cycle, and diffusional exchange of metabolites between different compartments. The model was used to calculate the changes in metabolite profiles during the cardiac cycle, metabolite and energy fluxes in different cellular compartments at high workload (corresponding to the rate of oxygen consumption of 46 mu atoms of O.(g wet mass)-1.min-1) under varying conditions of restricted ADP diffusion across mitochondrial outer membrane and creatine kinase isoenzyme "switchoff." In the complete system, restricted diffusion of ADP across the outer mitochondrial membrane stabilizes phosphocreatine production in cardiac mitochondria and increases the role of the phosphocreatine shuttle in energy transport and respiration regulation. Selective inhibition of myoplasmic or mitochondrial creatine kinase (modeling the experiments with transgenic animals) results in "takeover" of their function by another, active creatine kinase isoenzyme. This mathematical modeling also shows that assumption of the creatine kinase equilibrium in the cell may only be a very rough approximation to the reality at increased workload. The mathematical model developed can be used as a basis for further quantitative analyses of energy fluxes in the cell and their regulation, particularly by adding modules for adenylate kinase, the glycolytic system, and other reactions of energy metabolism of the cell. Images FIGURE 7 FIGURE 2 FIGURE 7 PMID:9199806

  16. Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues.

    PubMed

    Thome, Joseph J C; Bickham, Kara L; Ohmura, Yoshiaki; Kubota, Masaru; Matsuoka, Nobuhide; Gordon, Claire; Granot, Tomer; Griesemer, Adam; Lerner, Harvey; Kato, Tomoaki; Farber, Donna L

    2016-01-01

    It is unclear how the immune response in early life becomes appropriately stimulated to provide protection while also avoiding excessive activation as a result of diverse new antigens. T cells are integral to adaptive immunity; mouse studies indicate that tissue localization of T cell subsets is important for both protective immunity and immunoregulation. In humans, however, the early development and function of T cells in tissues remain unexplored. We present here an analysis of lymphoid and mucosal tissue T cells derived from pediatric organ donors in the first two years of life, as compared to adult organ donors, revealing early compartmentalization of T cell differentiation and regulation. Whereas adult tissues contain a predominance of memory T cells, in pediatric blood and tissues the main subset consists of naive recent thymic emigrants, with effector memory T cells (T(EM)) found only in the lungs and small intestine. Additionally, regulatory T (T(reg)) cells comprise a high proportion (30-40%) of CD4(+) T cells in pediatric tissues but are present at much lower frequencies (1-10%) in adult tissues. Pediatric tissue T(reg) cells suppress endogenous T cell activation, and early T cell functionality is confined to the mucosal sites that have the lowest T(reg):T(EM) cell ratios, which suggests control in situ of immune responses in early life. PMID:26657141

  17. GPU-Accelerated Compartmental Modeling Analysis of DCE-MRI Data from Glioblastoma Patients Treated with Bevacizumab

    PubMed Central

    Hsu, Yu-Han H.; Huang, Ziyin; Ferl, Gregory Z.; Ng, Chee M.

    2015-01-01

    The compartment model analysis using medical imaging data is the well-established but extremely time consuming technique for quantifying the changes in microvascular physiology of targeted organs in clinical patients after antivascular therapies. In this paper, we present a first graphics processing unit-accelerated method for compartmental modeling of medical imaging data. Using this approach, we performed the analysis of dynamic contrast-enhanced magnetic resonance imaging data from bevacizumab-treated glioblastoma patients in less than one minute per slice without losing accuracy. This approach reduced the computation time by more than 120-fold comparing to a central processing unit-based method that performed the analogous analysis steps in serial and more than 17-fold comparing to the algorithm that optimized for central processing unit computation. The method developed in this study could be of significant utility in reducing the computational times required to assess tumor physiology from dynamic contrast-enhanced magnetic resonance imaging data in preclinical and clinical development of antivascular therapies and related fields. PMID:25786263

  18. An in vitro compartmentalization-based method for the selection of bond-forming enzymes from large libraries.

    PubMed

    Gianella, Paul; Snapp, Erik L; Levy, Matthew

    2016-08-01

    We have developed a generalized in vitro compartmentalization-based bead display selection strategy that allows for the identification of enzymes that can perform ligation reactions. Although a number of methods have been developed to evolve such enzymes, many of them are limited in library size (10(6) -10(7) ), do not select for enzymes using a scheme that allows for multiple turnover, or only work on enzymes specific to nucleic acids. This approach is amenable to screening libraries of up to 10(12) protein variants by allowing beads to be overloaded with up to 10(4) unique mutants. Using this approach we isolated a variant of sortase A from Staphylococcus aureus that shows a 114-fold enhancement in kcat /KM in the absence of calcium compared to the wild-type and improved resistance to the inhibitory effects of cell lysates. Unlike the wild-type protein, the newly selected variant shows intracellular activity in the cytoplasm of eukaryotic cells where it may prove useful for intracellular labeling or synthetic biological applications. Biotechnol. Bioeng. 2016;113: 1647-1657. © 2016 Wiley Periodicals, Inc. PMID:26806853

  19. Inter-compartmental transport of organophosphate and pyrethroid pesticides in South China: implications for a regional risk assessment.

    PubMed

    Li, Huizhen; Wei, Yanli; Lydy, Michael J; You, Jing

    2014-07-01

    The dynamic flux of an organophosphate and four pyrethroid pesticides was determined in an air-(soil)-water-sediment system based on monitoring data from Guangzhou, China. The total air-water flux, including air-water gaseous exchange and atmospheric deposition, showed deposition from air to water for chlorpyrifos, bifenthrin and cypermethrin, but volatilization for lambda-cyhalothrin and permethrin. The transport of the pesticides from overlying water to sediment suggested that sediment acted as a sink for the pesticides. Additionally, distinct annual atmospheric depositional fluxes between legacy and current-use pesticides suggested the role of consumer usage in their transport throughout the system. Finally, pesticide toxicity was estimated from annual air-water-sediment flux within an urban stream in Guangzhou. A dynamic flux-based risk assessment indicated that inter-compartmental transport of chlorpyrifos decreased its atmospheric exposure, but had little influence on its aquatic toxicity. Instead, water-to-sediment transport of pyrethroids increased their sediment toxicity, which was supported by previously reported toxicity data. PMID:24704807

  20. Surface Interactions with Compartmentalized Cellular Phosphates Explain Rare Earth Oxide Nanoparticle Hazard and Provide Opportunities for Safer Design

    PubMed Central

    2014-01-01

    Growing international exploitation of rare earth oxides (REOs) for commercial and biological use has increased the possibility of human exposure and adverse health effects. Occupational exposure to rare earth materials in miners and polishers leads to a severe form of pneumoconiosis, while gadolinium-containing MRI contrast agents cause nephrogenic systemic fibrosis in patients with renal impairment. The mechanisms for inducing these adverse pro-fibrogenic effects are of considerable importance for the safety assessment of REO particles as well as presenting opportunities for safer design. In this study, using a well-prepared REO library, we obtained a mechanistic understanding of how REOs induce cellular and pulmonary damage by a compartmentalized intracellular biotransformation process in lysosomes that results in pro-fibrogenic growth factor production and lung fibrosis. We demonstrate that rare earth oxide ion shedding in acidifying macrophage lysosomes leads to biotic phosphate complexation that results in organelle damage due to stripping of phosphates from the surrounding lipid bilayer. This results in nanoparticle biotransformation into urchin shaped structures and setting in motion a series of events that trigger NLRP3 inflammasome activation, IL-1β release, TGF-β1 and PDGF-AA production. However, pretreatment of REO nanoparticles with phosphate in a neutral pH environment prevents biological transformation and pro-fibrogenic effects. This can be used as a safer design principle for producing rare earth nanoparticles for biological use. PMID:24417322

  1. Lipid droplet-associated proteins (LDAPs) are involved in the compartmentalization of lipophilic compounds in plant cells.

    PubMed

    Gidda, Satinder K; Watt, Samantha; Collins-Silva, Jillian; Kilaru, Aruna; Arondel, Vincent; Yurchenko, Olga; Horn, Patrick J; James, Christopher N; Shintani, David; Ohlrogge, John B; Chapman, Kent D; Mullen, Robert T; Dyer, John M

    2013-11-01

    While lipid droplets have traditionally been considered as inert sites for the storage of triacylglycerols and sterol esters, they are now recognized as dynamic and functionally diverse organelles involved in energy homeostasis, lipid signaling, and stress responses. Unlike most other organelles, lipid droplets are delineated by a half-unit membrane whose protein constituents are poorly understood, except in the specialized case of oleosins, which are associated with seed lipid droplets. Recently, we identified a new class of lipid-droplet associated proteins called LDAPs that localize specifically to the lipid droplet surface within plant cells and share extensive sequence similarity with the small rubber particle proteins (SRPPs) found in rubber-accumulating plants. Here, we provide additional evidence for a role of LDAPs in lipid accumulation in oil-rich fruit tissues, and further explore the functional relationships between LDAPs and SRPPs. In addition, we propose that the larger LDAP/SRPP protein family plays important roles in the compartmentalization of lipophilic compounds, including triacylglycerols and polyisoprenoids, into lipid droplets within plant cells. Potential roles in lipid droplet biogenesis and function of these proteins also are discussed. PMID:24305619

  2. Meta-Analysis of Arabidopsis thaliana Phospho-Proteomics Data Reveals Compartmentalization of Phosphorylation Motifs[C][W

    PubMed Central

    van Wijk, Klaas J.; Friso, Giulia; Walther, Dirk; Schulze, Waltraud X.

    2014-01-01

    Protein (de)phosphorylation plays an important role in plants. To provide a robust foundation for subcellular phosphorylation signaling network analysis and kinase-substrate relationships, we performed a meta-analysis of 27 published and unpublished in-house mass spectrometry–based phospho-proteome data sets for Arabidopsis thaliana covering a range of processes, (non)photosynthetic tissue types, and cell cultures. This resulted in an assembly of 60,366 phospho-peptides matching to 8141 nonredundant proteins. Filtering the data for quality and consistency generated a set of medium and a set of high confidence phospho-proteins and their assigned phospho-sites. The relation between single and multiphosphorylated peptides is discussed. The distribution of p-proteins across cellular functions and subcellular compartments was determined and showed overrepresentation of protein kinases. Extensive differences in frequency of pY were found between individual studies due to proteomics and mass spectrometry workflows. Interestingly, pY was underrepresented in peroxisomes but overrepresented in mitochondria. Using motif-finding algorithms motif-x and MMFPh at high stringency, we identified compartmentalization of phosphorylation motifs likely reflecting localized kinase activity. The filtering of the data assembly improved signal/noise ratio for such motifs. Identified motifs were linked to kinases through (bioinformatic) enrichment analysis. This study also provides insight into the challenges/pitfalls of using large-scale phospho-proteomic data sets to nonexperts. PMID:24894044

  3. Two-compartmental population balance modeling of a pulsed spray fluidized bed granulation based on computational fluid dynamics (CFD) analysis.

    PubMed

    Liu, Huolong; Li, Mingzhong

    2014-11-20

    In this work a two-compartmental population balance model (TCPBM) was proposed to model a pulsed top-spray fluidized bed granulation. The proposed TCPBM considered the spatially heterogeneous granulation mechanisms of the granule growth by dividing the granulator into two perfectly mixed zones of the wetting compartment and drying compartment, in which the aggregation mechanism was assumed in the wetting compartment and the breakage mechanism was considered in the drying compartment. The sizes of the wetting and drying compartments were constant in the TCPBM, in which 30% of the bed was the wetting compartment and 70% of the bed was the drying compartment. The exchange rate of particles between the wetting and drying compartments was determined by the details of the flow properties and distribution of particles predicted by the computational fluid dynamics (CFD) simulation. The experimental validation has shown that the proposed TCPBM can predict evolution of the granule size and distribution within the granulator under different binder spray operating conditions accurately. PMID:25181553

  4. High content of creatine kinase in chicken retina: compartmentalized localization of creatine kinase isoenzymes in photoreceptor cells.

    PubMed Central

    Wallimann, T; Wegmann, G; Moser, H; Huber, R; Eppenberger, H M

    1986-01-01

    Two isoforms of creatine kinase (CK; ATP:creatine N-phosphotransferase, E.C. 2.7.3.2), brain type (BB-CK) and mitochondrial type (MiMi-CK), but not the muscle types (MM- or hybrid MB-CK), were identified by cellulose polyacetate electrophoresis and immunoblots in retina from adult chickens. Indirect immunofluorescence labeling of cryosections of retinas revealed high concentrations of BB-CK in both rod and cone photoreceptor cells. Most of the fluorescence staining with anti-B-CK antibodies was found within the myoid and the ellipsoid portions of inner segments and the peripheral region of the outer segments. Significant staining with anti-B-CK antibodies was also found in horizontal cells and in the optical nerve fibers, with additional stratified staining in the inner plexiform layer. MiMi-CK was solely demonstrated in the ellipsoid portion of the photoreceptor cells. The presence of high concentrations of compartmentalized CK isoenzymes within photoreceptor cells (approximately equal to 30 enzyme units/mg) as well as the relatively high concentration of total creatine in these cells (approximately equal to 10-15 mM) indicates an important physiological function for CK and phosphocreatine in the energy transduction of vision. Images PMID:3520556

  5. Is the Dissociative Experiences Scale able to identify detachment and compartmentalization symptoms? Factor structure of the Dissociative Experiences Scale in a large sample of psychiatric and nonpsychiatric subjects

    PubMed Central

    Mazzotti, Eva; Farina, Benedetto; Imperatori, Claudio; Mansutti, Federica; Prunetti, Elena; Speranza, Anna Maria; Barbaranelli, Claudio

    2016-01-01

    Background In this study, we explored the ability of the Dissociative Experiences Scale (DES) to catch detachment and compartmentalization symptoms. Participants and methods The DES factor structure was evaluated in 768 psychiatric patients (546 women and 222 men) and in 2,403 subjects enrolled in nonpsychiatric settings (1,857 women and 546 men). All participants were administered the Italian version of DES. Twenty senior psychiatric experts in the treatment of dissociative symptoms independently assessed the DES items and categorized each of them as follows: “C” for compartmentalization, “D” for detachment, and “NC” for noncongruence with either C or D. Results Confirmatory factor analysis supported the three-factor structure of DES in both clinical and nonclinical samples and its invariance across the two groups. Moreover, factor analyses results overlapped with those from the expert classification procedure. Conclusion Our results showed that DES can be used as a valid instrument for clinicians to assess the frequency of different types of dissociative experiences including detachment and compartmentalization. PMID:27350746

  6. Compartmentalized Cyclic Adenosine 3′,5′-Monophosphate at the Plasma Membrane Clusters PDE3A and Cystic Fibrosis Transmembrane Conductance Regulator into Microdomains

    PubMed Central

    Penmatsa, Himabindu; Zhang, Weiqiang; Yarlagadda, Sunitha; Li, Chunying; Conoley, Veronica G.; Yue, Junming; Bahouth, Suleiman W.; Buddington, Randal K.; Zhang, Guangping; Nelson, Deborah J.; Sonecha, Monal D.; Manganiello, Vincent; Wine, Jeffrey J.

    2010-01-01

    Formation of multiple-protein macromolecular complexes at specialized subcellular microdomains increases the specificity and efficiency of signaling in cells. In this study, we demonstrate that phosphodiesterase type 3A (PDE3A) physically and functionally interacts with cystic fibrosis transmembrane conductance regulator (CFTR) channel. PDE3A inhibition generates compartmentalized cyclic adenosine 3′,5′-monophosphate (cAMP), which further clusters PDE3A and CFTR into microdomains at the plasma membrane and potentiates CFTR channel function. Actin skeleton disruption reduces PDE3A–CFTR interaction and segregates PDE3A from its interacting partners, thus compromising the integrity of the CFTR-PDE3A–containing macromolecular complex. Consequently, compartmentalized cAMP signaling is lost. PDE3A inhibition no longer activates CFTR channel function in a compartmentalized manner. The physiological relevance of PDE3A–CFTR interaction was investigated using pig trachea submucosal gland secretion model. Our data show that PDE3A inhibition augments CFTR-dependent submucosal gland secretion and actin skeleton disruption decreases secretion. PMID:20089840

  7. Elevated compartmentalization of Na+ into vacuoles improves salt and cold stress tolerance in sweet potato (Ipomoea batatas).

    PubMed

    Fan, Weijuan; Deng, Gaifang; Wang, Hongxia; Zhang, Hongxia; Zhang, Peng

    2015-08-01

    Salinity and low temperature are the main limiting factors for sweet potato (Ipomoea batatas) growth and agricultural productivity. Various studies have shown that plant NHX-type antiporter plays a crucial role in regulating plant tolerance to salt stress by intracellular Na(+) compartmentalization. The Arabidopsis thaliana AtNHX1 gene that encodes a vacuolar Na(+) /H(+) antiporter was introduced into the sweet potato cultivar Xushu-22 by Agrobacterium-mediated transformation to confer abiotic stress tolerance. Stable insertion of AtNHX1 into the sweet potato genome and its expression was confirmed by Southern blot and reverse transcription-polymerase chain reaction (RT-PCR). A remarkably higher Na(+) /H(+) exchange activity of tonoplast membrane from transgenic sweet potato lines (NOE) in comparison with wild-type (WT) plants confirmed the vacuolar antiporter function in mediating Na(+) /H(+) exchange. Under salt stress, NOE plants accumulated higher Na(+) and K(+) levels in their tissues compared with WT plants, maintaining high K(+) /Na(+) ratios. Consequently, NOE plants showed enhanced protection against cell damage due to the increased proline accumulation, preserved cell membrane integrity, enhanced reactive oxygen species (ROS) scavenging (e.g. increased superoxide dismutase activity), and reduced H2 O2 and malondialdehyde (MDA) production. Moreover, the transgenic plants showed improved cold tolerance through multiple mechanisms of action, revealing the first molecular evidence for NHX1 function in cold response. The transgenic plants showed better biomass production and root yield under stressful conditions. These findings demonstrate that overexpressing AtNHX1 in sweet potato renders the crop tolerant to both salt and cold stresses, providing a greater capacity for the use of AtNHX1 in improving crop performance under combined abiotic stress conditions. PMID:25307930

  8. Co-compartmentalization of MAP kinases and cytosolic phospholipase A2 at cytoplasmic arachidonate-rich lipid bodies.

    PubMed Central

    Yu, W.; Bozza, P. T.; Tzizik, D. M.; Gray, J. P.; Cassara, J.; Dvorak, A. M.; Weller, P. F.

    1998-01-01

    Lipid bodies are inducible lipid domains abundantly present in leukocytes engaged in inflammation. They are rich in esterified arachidonate and are also potential sites for eicosanoid-forming enzyme localization. It is therefore of interest to know whether arachidonate-releasing cytosolic phospholipase A2 (cPLA2) localizes at lipid bodies. Here, we present evidence that cPLA2 and its activating protein kinases, mitogen-activated protein (MAP) kinases, co-localize at lipid bodies. U937 cells express high levels of cPLA2 and contain numerous cytoplasmic lipid bodies. Using double-labeling immunocytochemistry we demonstrated punctate cytoplasmic localizations of both cPLA2 and MAP kinases in U937 cells that were perfectly concordant with fluorescent fatty-acid-labeled lipid bodies. The co-localization of cPLA2 and MAP kinases at lipid bodies was confirmed by subcellular fractionation and immunoblot. Lipid body fractions free of cytosol and other organelles contained significant amounts of [14C]arachidonate-labeled phosphatidylcholine and cPLA2 enzymatic activities. Immunoblotting with specific antibodies identified cPLA2 as well as MAP kinases, including ERK1, ERK2, p85, and p38, in lipid bodies. The co-compartmentalization within arachidonate-rich lipid bodies of cPLA2 and its potentially activating protein kinases suggests that lipid bodies may be structurally distinct intracellular sites active in extracellular ligand-induced arachidonate release and eicosanoid formation. Images Figure 1 Figure 2 Figure 3 Figure 6 Figure 7 PMID:9502418

  9. High-resolution sequence stratigraphy of Late Mississippian carbonates in the Appalachian basin, implications for compartmentalization of reservoir facies

    SciTech Connect

    Al-Tawil, A.; Read, J.F. )

    1996-01-01

    The Late Mississippian Newman/Greenbrier carbonates were deposited in the Appalachian foreland basin whose depocenter lay to the south and east of Kentucky, West Virginia and Virginia. Over 50 closely spaced detailed measured sections along with numerous wireline logs, biostratigraphic data, and lithologic markers are used to construct detailed facies cross-sections. In the Newman limestone along the Cincinnati Arch, four sequences bounded by regional unconformities can be recognized. The lower three sequences contain one to eight oolite bearing disconformity bounded parasequences. Parasequences within sequences one to three, progressively onlap the Waverly and Cincinnati arches. These are dominated by shoal water ooid grainstone and lagoonal skeletal wackestone/mudstone facies, while eolianite quartzose peloidal grainstone facies are restricted to the lower two sequences. Sequence four is thicker and capped by a disconformity, but is internally conformable. It contains thick oolite units in the lower part (up to 10 m), open ramp skeletal packstone and shale (2nd order maximum flooding of the studied interval). In the much thicker foreland basin sections in West Virginia, four sequences also can be defined. The lowstand deposits are characterized by red beds up-dip, locally thickened tidal flat facies down-dip, and thin grainstone tongues extending into the slope/basin facies. Within the sequences, parasequences lack bounding disconformities, and are dominated by open ramp skeletal packstone and shoal water ooid grainstone facies. Eolianite facies are common in landward parts of the lower two sequences. The complex regional distribution and vertical compartmentalization of these multilateral oolitic reservoirs in both areas on this tropical ramp reflect tidal bar morphologies, differential regional subsidence patterns, coupled with 4th order moderate amplitude eustacy.

  10. High-resolution sequence stratigraphy of Late Mississippian carbonates in the Appalachian basin, implications for compartmentalization of reservoir facies

    SciTech Connect

    Al-Tawil, A.; Read, J.F.

    1996-12-31

    The Late Mississippian Newman/Greenbrier carbonates were deposited in the Appalachian foreland basin whose depocenter lay to the south and east of Kentucky, West Virginia and Virginia. Over 50 closely spaced detailed measured sections along with numerous wireline logs, biostratigraphic data, and lithologic markers are used to construct detailed facies cross-sections. In the Newman limestone along the Cincinnati Arch, four sequences bounded by regional unconformities can be recognized. The lower three sequences contain one to eight oolite bearing disconformity bounded parasequences. Parasequences within sequences one to three, progressively onlap the Waverly and Cincinnati arches. These are dominated by shoal water ooid grainstone and lagoonal skeletal wackestone/mudstone facies, while eolianite quartzose peloidal grainstone facies are restricted to the lower two sequences. Sequence four is thicker and capped by a disconformity, but is internally conformable. It contains thick oolite units in the lower part (up to 10 m), open ramp skeletal packstone and shale (2nd order maximum flooding of the studied interval). In the much thicker foreland basin sections in West Virginia, four sequences also can be defined. The lowstand deposits are characterized by red beds up-dip, locally thickened tidal flat facies down-dip, and thin grainstone tongues extending into the slope/basin facies. Within the sequences, parasequences lack bounding disconformities, and are dominated by open ramp skeletal packstone and shoal water ooid grainstone facies. Eolianite facies are common in landward parts of the lower two sequences. The complex regional distribution and vertical compartmentalization of these multilateral oolitic reservoirs in both areas on this tropical ramp reflect tidal bar morphologies, differential regional subsidence patterns, coupled with 4th order moderate amplitude eustacy.

  11. New Insight into the Mechanism of Accumulation and Intraerythrocytic Compartmentation of Albitiazolium, a New Type of Antimalarial

    PubMed Central

    Tran Van Ba, Christophe; Maynadier, Marjorie; Bordat, Yann; Perez, Julie; Peyrottes, Suzanne; Fraisse, Laurent

    2014-01-01

    Bis-thiazolium salts constitute a new class of antihematozoan drugs that inhibit parasite phosphatidylcholine biosynthesis. They specifically accumulate in Plasmodium- and Babesia-infected red blood cells (IRBC). Here, we provide new insight into the choline analogue albitiazolium, which is currently being clinically tested against severe malaria. Concentration-dependent accumulation in P. falciparum-infected erythrocytes reached steady state after 90 to 120 min and was massive throughout the blood cycle, with cellular accumulation ratios of up to 1,000. This could not occur through a lysosomotropic effect, and the extent did not depend on the food vacuole pH, which was the case for the weak base chloroquine. Analysis of albitiazolium accumulation in P. falciparum IRBC revealed a high-affinity component that was restricted to mature stages and suppressed by pepstatin A treatment, and thus likely related to drug accumulation in the parasite food vacuole. Albitiazolium also accumulated in a second high-capacity component present throughout the blood cycle that was likely not related to the food vacuole and also observed with Babesia divergens-infected erythrocytes. Accumulation was strictly glucose dependent, drastically inhibited by H+/K+ and Na+ ionophores upon collapse of ionic gradients, and appeared to be energized by the proton-motive force across the erythrocyte plasma membrane, indicating the importance of transport steps for this permanently charged new type of antimalarial agent. This specific, massive, and irreversible accumulation allows albitiazolium to restrict its toxicity to hematozoa-infected erythrocytes. The intraparasitic compartmentation of albitiazolium corroborates a dual mechanism of action, which could make this new type of antimalarial agent resistant to parasite resistance. PMID:25001307

  12. Compartmental Targeting for mTHPC-Based Photodynamic Treatment In Vivo: Correlation of Efficiency, Pharmacokinetics, and Regional Distribution of Apoptosis

    SciTech Connect

    Garrier, Julie; Bressenot, Aude; Graefe, Susanna

    2010-10-01

    Purpose: The present study investigates the efficacy of compartmental targeting in xenografted tumors treated by meta-tetra(hydroxyphenyl)chlorin (mTHPC)-mediated photodynamic therapy (PDT). The therapeutic efficacy was, furthermore, related to a regional photoinduced distribution of apoptosis and an mTHPC biodistribution profile. Methods and Materials: Mice bearing EMT6 tumors were subjected to a single irradiation (10 J/cm{sup 2}) of red laser light (652 nm) at different intervals after a single- (0.3 mg/kg or 0.15 mg/kg) or double-intravenous (2 x 0.15 mg/kg) injection(s) of mTHPC. Efficiency of the treatment was evaluated by monitoring tumor regrowth. mTHPC pharmacokinetics were assessed by high-performance liquid chromatography analysis of excised organs. The regional distribution of apoptosis in tumor sections was investigated with a newly developed colabelling immunohistochemistry technique. Results: A fractionated double-injection protocol of mTHPC with 24-h and 3-h drug-light intervals (DLI) yielded 100% tumor cure, with tumors presenting a massive apoptosis of neoplastic cells along with a distortion of vessels. The best efficiency for a single injection (0.3 mg/kg) was about 54% tumor cure and corresponded to a DLI of 3 h. At this DLI, tumors showed apoptosis of endothelial cells in residual vessels. Concentrations of mTHPC observed in plasma and tumor for the fractionated injection were not statistically different and were less than the total drug dose in each compartment. Conclusions: The present work suggests that clinical PDT protocols with mTHPC could be greatly improved by fractionation of the drug administration. Time points should be chosen based on the intratumoral spatiotemporal drug distribution.

  13. Ferrocene-based compartmental ligand for the assembly of neutral Zn(II)/Ln(III) heterometallic complexes.

    PubMed

    Chandrasekhar, Vadapalli; Chakraborty, Amit; Sañudo, E Carolina

    2013-10-01

    A ferrocene-based compartmental ligand, H2L, was synthesized by the reaction of diacetyl ferrocene with hydrazine hydrate followed by a condensation reaction with o-vanillin. [L](2-) possesses a dual coordination pocket, an inner pocket of 2 imino nitrogens and two phenolate oxygens and an outer pocket of two phenolate and two methoxy oxygen atoms. Utilizing this ligand, several Zn(II)/Ln(III) heterobimetallic complexes were assembled: [LZn(μ-OAc)Dy(NO3)2] (2), [LZn(μ-OAc)Tb(NO3)2] (3), [LZn(μ-OAc)Gd(NO3)2·2CHCl3] (4), [LZn(μ-OAc)Er(NO3)2] (5), [LZn(μ-OAc)Ho(NO3)2] (6), [LZn(μ-OAc)Eu(NO3)2] (7). All of these metal complexes are neutral and isostructural: the Zn(II) ion occupies the inner coordination pocket while the Ln(III) ion occupies the outer coordination pocket of the doubly deprotonated ligand [L](2-). Zn(II) has a coordination number of 5 (2N, 3O) in a square pyramidal coordination geometry while Ln(III) has a coordination number of 9 (9O) in a distorted tricapped trigonal prismatic geometry. Zn(II) and the 4f metal ion are bridged to each other by two phenolate oxygen atoms and an acetate ligand. ESI-MS reveals that 2-7 retain their structural integrity in solution. Cyclic voltammetry of 1-7 revealed a quasi-reversible oxidation (involving the ferrocene motif) and an irreversible reduction of the hydrazone unit. Magnetic studies of 2, 3 and 6 were carried out. Ac susceptibility studies did not reveal slow relaxation of magnetization. PMID:23893198

  14. Development of a Novel Oral Cavity Compartmental Absorption and Transit Model for Sublingual Administration: Illustration with Zolpidem.

    PubMed

    Xia, Binfeng; Yang, Zhen; Zhou, Haiying; Lukacova, Viera; Zhu, Wei; Milewski, Mikolaj; Kesisoglou, Filippos

    2015-05-01

    Intraoral (IO) delivery is an alternative administration route to deliver a drug substance via the mouth that provides several advantages over conventional oral dosage forms. The purpose of this work was to develop and evaluate a novel, physiologically based oral cavity model for projection and mechanistic analysis of the clinical pharmacokinetics of intraoral formulations. The GastroPlus™ Oral Cavity Compartmental Absorption and Transit (OCCAT™) model was used to simulate the plasma concentration versus time profiles and the fraction and rate of intraoral drug transit/absorption for Intermezzo® sublingual tablets (zolpidem tartrate). The model was evaluated by the goodness-of-fit between simulated and observed concentrations and the deviation of key PK parameters (e.g., C max, T max, and AUC). In addition, a sensitivity analysis was conducted to demonstrate the interplay and impact of key modeling parameters on the fraction absorbed via oral mucosa (F a_IO). The OCCAT™ model captured the observed pharmacokinetics for Intermezzo® sublingual tablets (R (2) > 0.9). The predicted deviations (%) for C max, AUC0-inf, AUC0-20 min, and T max were 5.7, 28.0, 11.8, and 28.6%, respectively, indicating good prediction accuracy. The model also estimated ~18% of total drug was absorbed via the IO route. Furthermore, the sensitivity analysis indicated that the F a_IO was not only associated with drug diffusivity and unbound fraction in epithelium tissue (f ut) but also depended on the physicochemical properties of compounds for IO delivery (e.g., solubility and logD pH = 7.4). The novel physiologically based IO absorption OCCAT™ model showed satisfactory performance and will be helpful to guide development of future intraoral formulations. PMID:25716146

  15. Compartmentalization of simian immunodeficiency virus replication within secondary lymphoid tissues of rhesus macaques is linked to disease stage and inversely related to localization of virus-specific CTL.

    PubMed

    Connick, Elizabeth; Folkvord, Joy M; Lind, Katherine T; Rakasz, Eva G; Miles, Brodie; Wilson, Nancy A; Santiago, Mario L; Schmitt, Kimberly; Stephens, Edward B; Kim, Hyeon O; Wagstaff, Reece; Li, Shengbin; Abdelaal, Hadia M; Kemp, Nathan; Watkins, David I; MaWhinney, Samantha; Skinner, Pamela J

    2014-12-01

    We previously demonstrated that HIV replication is concentrated in lymph node B cell follicles during chronic infection and that HIV-specific CTL fail to accumulate in large numbers at those sites. It is unknown whether these observations can be generalized to other secondary lymphoid tissues or whether virus compartmentalization occurs in the absence of CTL. We evaluated these questions in SIVmac239-infected rhesus macaques by quantifying SIV RNA(+) cells and SIV-specific CTL in situ in spleen, lymph nodes, and intestinal tissues obtained at several stages of infection. During chronic asymptomatic infection prior to simian AIDS, SIV-producing cells were more concentrated in follicular (F) compared with extrafollicular (EF) regions of secondary lymphoid tissues. At day 14 of infection, when CTL have minimal impact on virus replication, there was no compartmentalization of SIV-producing cells. Virus compartmentalization was diminished in animals with simian AIDS, which often have low-frequency CTL responses. SIV-specific CTL were consistently more concentrated within EF regions of lymph node and spleen in chronically infected animals regardless of epitope specificity. Frequencies of SIV-specific CTL within F and EF compartments predicted SIV RNA(+) cells within these compartments in a mixed model. Few SIV-specific CTL expressed the F homing molecule CXCR5 in the absence of the EF retention molecule CCR7, possibly accounting for the paucity of F CTL. These findings bolster the hypothesis that B cell follicles are immune privileged sites and suggest that strategies to augment CTL in B cell follicles could lead to improved viral control and possibly a functional cure for HIV infection. PMID:25362178

  16. Compartmentalized replication of R5 T cell-tropic HIV-1 in the central nervous system early in the course of infection.

    PubMed

    Sturdevant, Christa Buckheit; Joseph, Sarah B; Schnell, Gretja; Price, Richard W; Swanstrom, Ronald; Spudich, Serena

    2015-03-01

    Compartmentalized HIV-1 replication within the central nervous system (CNS) likely provides a foundation for neurocognitive impairment and a potentially important tissue reservoir. The timing of emergence and character of this local CNS replication has not been defined in a population of subjects. We examined the frequency of elevated cerebrospinal fluid (CSF) HIV-1 RNA concentration, the nature of CSF viral populations compared to the blood, and the presence of a cellular inflammatory response (with the potential to bring infected cells into the CNS) using paired CSF and blood samples obtained over the first two years of infection from 72 ART-naïve subjects. Using single genome amplification (SGA) and phylodynamics analysis of full-length env sequences, we compared CSF and blood viral populations in 33 of the 72 subjects. Independent HIV-1 replication in the CNS (compartmentalization) was detected in 20% of sample pairs analyzed by SGA, or 7% of all sample pairs, and was exclusively observed after four months of infection. In subjects with longitudinal sampling, 30% showed evidence of CNS viral replication or pleocytosis/inflammation in at least one time point, and in approximately 16% of subjects we observed evolving CSF/CNS compartmentalized viral replication and/or a marked CSF inflammatory response at multiple time points suggesting an ongoing or recurrent impact of the infection in the CNS. Two subjects had one of two transmitted lineages (or their recombinant) largely sequestered within the CNS shortly after transmission, indicating an additional mechanism for establishing early CNS replication. Transmitted variants were R5 T cell-tropic. Overall, examination of the relationships between CSF viral populations, blood and CSF HIV-1 RNA concentrations, and inflammatory responses suggested four distinct states of viral population dynamics, with associated mechanisms of local viral replication and the early influx of virus into the CNS. This study considerably

  17. Subcellular compartmentalization of Cd and Zn in two bivalves. I. Significance of metal-sensitive fractions (MSF) and biologically detoxified metal (BDM)

    USGS Publications Warehouse

    Wallace, W.G.; Lee, B.-G.; Luoma, S.N.

    2003-01-01

    Many aspects of metal accumulation in aquatic invertebrates (i.e. toxicity, tolerance and trophic transfer) can be understood by examining the subcellular partitioning of accumulated metal. In this paper, we use a compartmentalization approach to interpret the significance of metal, species and size dependence in the subcellular partitioning of Cd and Zn in the bivalves Macoma balthica and Potamocorbula amurensis. Of special interest is the compartmentalization of metal as metal-sensitive fractions (MSF) (i.e. organelles and heat-sensitive proteins, termed 'enzymes' hereafter) and biologically detoxified metal (BDM) (i.e. metallothioneins [MT] and metal-rich granules [MRG]). Clams from San Francisco Bay, CA, were exposed for 14 d to seawater (20??? salinity) containing 3.5 ??g l-1 Cd and 20.5 ??g l-1 Zn, including 109Cd and 65Zn as radiotracers. Uptake was followed by 21 d of depuration. The subcellular partitioning of metal within clams was examined following exposure and loss. P. amurensis accumulated ???22x more Cd and ???2x more Zn than M. balthica. MT played an important role in the storage of Cd in P. amurensis, while organelles were the major site of Zn accumulation. In M. balthica, Cd and Zn partitioned similarly, although the pathway of detoxification was metal-specific (MRG for Cd; MRG and MT for Zn). Upon loss, M. balthica depurated ???40% of Cd with Zn being retained; P. amurensis retained Cd and depurated Zn (???40%). During efflux, Cd and Zn concentrations in the MSF compartment of both clams declined with metal either being lost from the animal or being transferred to the BDM compartment. Subcellular compartmentalization was also size-dependent, with the importance of BDM increasing with clam size; MSF decreased accordingly. We hypothesized that progressive retention of metal as BDM (i.e. MRG) with age may lead to size dependency of metal concentrations often observed in some populations of M. balthica.

  18. Non-stationary 13C metabolic flux analysis of Chinese hamster ovary cells in batch culture using extracellular labeling highlights metabolic reversibility and compartmentation

    PubMed Central

    2014-01-01

    Background Mapping the intracellular fluxes for established mammalian cell lines becomes increasingly important for scientific and economic reasons. However, this is being hampered by the high complexity of metabolic networks, particularly concerning compartmentation. Results Intracellular fluxes of the CHO-K1 cell line central carbon metabolism were successfully determined for a complex network using non-stationary 13C metabolic flux analysis. Mass isotopomers of extracellular metabolites were determined using [U-13C6] glucose as labeled substrate. Metabolic compartmentation and extracellular transport reversibility proved essential to successfully reproduce the dynamics of the labeling patterns. Alanine and pyruvate reversibility changed dynamically even if their net production fluxes remained constant. Cataplerotic fluxes of cytosolic phosphoenolpyruvate carboxykinase and mitochondrial malic enzyme and pyruvate carboxylase were successfully determined. Glycolytic pyruvate channeling to lactate was modeled by including a separate pyruvate pool. In the exponential growth phase, alanine, glycine and glutamate were excreted, and glutamine, aspartate, asparagine and serine were taken up; however, all these amino acids except asparagine were exchanged reversibly with the media. High fluxes were determined in the pentose phosphate pathway and the TCA cycle. The latter was fueled mainly by glucose but also by amino acid catabolism. Conclusions The CHO-K1 central metabolism in controlled batch culture proves to be robust. It has the main purpose to ensure fast growth on a mixture of substrates and also to mitigate oxidative stress. It achieves this by using compartmentation to control NADPH and NADH availability and by simultaneous synthesis and catabolism of amino acids. PMID:24773761

  19. Reduced Genetic Diversity in Lymphoid and Central Nervous System Tissues and Selection-Induced Tissue-Specific Compartmentalization of Neuropathogenic SIVsmmFGb during Acute Infection

    PubMed Central

    Reeve, Aaron B.; Patel, Kalpana; Pearce, Nicholas C.; Augustus, Katherine V.; Domingues, Heber G.; O'Neil, Shawn P.

    2009-01-01

    Abstract The simian lentivirus strain SIVsmmFGb is a viral swarm population inducing neuropathology in over 90% of infected pigtailed macaques and serves as a reliable model for HIV neuropathogenesis. However, little is understood about the genetic diversity of this virus, how said diversity influences the initial seeding of the central nervous system and lymph nodes, or whether the virus forms distinct genetic compartments between tissues during acute infection. In this study, we establish that our SIVsmmFGb stock virus contains four genetically distinct envelope V1 region groups, three distinct integrase groups, and two Nef groups. We demonstrate that initial central nervous system and lymph node seeding reduces envelope V1 and integrase genetic diversity but has a variable effect on Nef diversity. SIVsmmFGb envelope V1 region genes from the basal ganglia, cerebellum, and hippocampus form distinct genetic compartments from each other, the midfrontal cortex, and the lymph nodes. Basal ganglia, cerebellum, hippocampus, and midfrontal cortex-derived nef genes all form distinct genetic compartments from each other, as well as from the lymph nodes. We also find basal ganglia, hippocampus, and midfrontal cortex-derived integrase sequences forming distinct compartments from both of the lymph nodes and that the hippocampus and midfrontal cortex form separate compartments from the cerebellum, while the axillary and mesenteric lymph nodes compartmentalize separately from each other. Compartmentalization of the envelope V1 genes resulted from positive selection, and compartmentalization of the nef and integrase genes from negative selection. These results indicate restrictions on virus genetic diversity during initial tissue seeding in neuropathogenic SIV infection. PMID:19500015

  20. Double-input compartmental modeling and spectral analysis for the quantification of positron emission tomography data in oncology

    NASA Astrophysics Data System (ADS)

    Tomasi, G.; Kimberley, S.; Rosso, L.; Aboagye, E.; Turkheimer, F.

    2012-04-01

    In positron emission tomography (PET) studies involving organs different from the brain, ignoring the metabolite contribution to the tissue time-activity curves (TAC), as in the standard single-input (SI) models, may compromise the accuracy of the estimated parameters. We employed here double-input (DI) compartmental modeling (CM), previously used for [11C]thymidine, and a novel DI spectral analysis (SA) approach on the tracers 5-[18F]fluorouracil (5-[18F]FU) and [18F]fluorothymidine ([18F]FLT). CM and SA were performed initially with a SI approach using the parent plasma TAC as an input function. These methods were then employed using a DI approach with the metabolite plasma TAC as an additional input function. Regions of interest (ROIs) corresponding to healthy liver, kidneys and liver metastases for 5-[18F]FU and to tumor, vertebra and liver for [18F]FLT were analyzed. For 5-[18F]FU, the improvement of the fit quality with the DI approaches was remarkable; in CM, the Akaike information criterion (AIC) always selected the DI over the SI model. Volume of distribution estimates obtained with DI CM and DI SA were in excellent agreement, for both parent 5-[18F]FU (R2 = 0.91) and metabolite [18F]FBAL (R2 = 0.99). For [18F]FLT, the DI methods provided notable improvements but less substantial than for 5-[18F]FU due to the lower rate of metabolism of [18F]FLT. On the basis of the AIC values, agreement between [18F]FLT Ki estimated with the SI and DI models was good (R2 = 0.75) for the ROIs where the metabolite contribution was negligible, indicating that the additional input did not bias the parent tracer only-related estimates. When the AIC suggested a substantial contribution of the metabolite [18F]FLT-glucuronide, on the other hand, the change in the parent tracer only-related parameters was significant (R2 = 0.33 for Ki). Our results indicated that improvements of DI over SI approaches can range from moderate to substantial and are more significant for tracers with

  1. Photosynthetic Characteristics of Portulaca grandiflora, a Succulent C(4) Dicot : CELLULAR COMPARTMENTATION OF ENZYMES AND ACID METABOLISM.

    PubMed

    Ku, S B; Shieh, Y J; Reger, B J; Black, C C

    1981-11-01

    The succulent, cylindrical leaves of the C(4) dicot Portulaca grandiflora possess three distinct green cell types: bundle sheath cells (BSC) in radial arrangement around the vascular bundles; mesophyll cells (MC) in an outer layer adjacent to the BSC; and water storage cells (WSC) in the leaf center. Unlike typical Kranz leaf anatomy, the MC do not surround the bundle sheath tissue but occur only in the area between the bundle sheath and the epidermis. Intercellular localization of photosynthetic enzymes was characterized using protoplasts isolated enzymatically from all three green cell types.Like other C(4) plants, P. grandiflora has ribulose 1,5-bisphosphate carboxylase and the decarboxylating enzyme, NADP(+)-malic enzyme, in the BSC. Unlike other C(4) plants, however, phosphoenolpyruvate carboxylase, pyruvate, Pi dikinase, and NADP(+)-malate dehydrogenase of the C(4) pathway were present in all three green cell types, indicating that all are capable of fixing CO(2) via phosphoenolpyruvate carboxylase and regenerating phosphoenolpyruvate. Other enzymes were about equally distributed between MC and BSC similar to other C(4) plants. The enzyme profile of the WSC was similar to that of the MC but with reduced activity in most enzymes, except mitochondrion-associated enzymes.Intracellular localization of enzymes was studied in organelles partitioned by differential centrifugation using mechanically ruptured mesophyll and bundle sheath protoplasts. Phosphoenolpyruvate carboxylase was a cytosolic enzyme in both cells; whereas, ribulose 1,5-bisphosphate carboxylase and NADP(+)-malic enzyme were exclusively compartmentalized in the bundle sheath chloroplasts. NADP(+)-malate dehydrogenase, pyruvate, Pi dikinase, aspartate aminotransferase, 3-phosphoglycerate kinase, and NADP(+)-triose-P dehydrogenase were predominantly localized in the chloroplasts while alanine aminotransferase and NAD(+)-malate dehydrogenase were mainly present in the cytosol of both cell types. Based

  2. Nuclear Medicine

    MedlinePlus

    ... Parents/Teachers Resource Links for Students Glossary Nuclear Medicine What is nuclear medicine? What are radioactive tracers? ... funded researchers advancing nuclear medicine? What is nuclear medicine? Nuclear medicine is a medical specialty that uses ...

  3. The Candidate Phylum Poribacteria by Single-Cell Genomics: New Insights into Phylogeny, Cell-Compartmentation, Eukaryote-Like Repeat Proteins, and Other Genomic Features

    PubMed Central

    Kamke, Janine; Rinke, Christian; Schwientek, Patrick; Mavromatis, Kostas; Ivanova, Natalia; Sczyrba, Alexander; Woyke, Tanja; Hentschel, Ute

    2014-01-01

    The candidate phylum Poribacteria is one of the most dominant and widespread members of the microbial communities residing within marine sponges. Cell compartmentalization had been postulated along with their discovery about a decade ago and their phylogenetic association to the Planctomycetes, Verrucomicrobia, Chlamydiae superphylum was proposed soon thereafter. In the present study we revised these features based on genomic data obtained from six poribacterial single cells. We propose that Poribacteria form a distinct monophyletic phylum contiguous to the PVC superphylum together with other candidate phyla. Our genomic analyses supported the possibility of cell compartmentalization in form of bacterial microcompartments. Further analyses of eukaryote-like protein domains stressed the importance of such proteins with features including tetratricopeptide repeats, leucin rich repeats as well as low density lipoproteins receptor repeats, the latter of which are reported here for the first time from a sponge symbiont. Finally, examining the most abundant protein domain family on poribacterial genomes revealed diverse phyH family proteins, some of which may be related to dissolved organic posphorus uptake. PMID:24498082

  4. Mechanisms of salt tolerance in habanero pepper plants (Capsicum chinense Jacq.): Proline accumulation, ions dynamics and sodium root-shoot partition and compartmentation

    PubMed Central

    Bojórquez-Quintal, Emanuel; Velarde-Buendía, Ana; Ku-González, Ángela; Carillo-Pech, Mildred; Ortega-Camacho, Daniela; Echevarría-Machado, Ileana; Pottosin, Igor; Martínez-Estévez, Manuel

    2014-01-01

    Despite its economic relevance, little is known about salt tolerance mechanisms in pepper plants. To address this question, we compared differences in responses to NaCl in two Capsicum chinense varieties: Rex (tolerant) and Chichen-Itza (sensitive). Under salt stress (150 mM NaCl over 7 days) roots of Rex variety accumulated 50 times more compatible solutes such as proline compared to Chichen-Itza. Mineral analysis indicated that Na+ is restricted to roots by preventing its transport to leaves. Fluorescence analysis suggested an efficient Na+ compartmentalization in vacuole-like structures and in small intracellular compartments in roots of Rex variety. At the same time, Na+ in Chichen-Itza plants was compartmentalized in the apoplast, suggesting substantial Na+ extrusion. Rex variety was found to retain more K+ in its roots under salt stress according to a mineral analysis and microelectrode ion flux estimation (MIFE). Vanadate-sensitive H+ efflux was higher in Chichen-Itza variety plants, suggesting a higher activity of the plasma membrane H+-ATPase, which fuels the extrusion of Na+, and, possibly, also the re-uptake of K+. Our results suggest a combination of stress tolerance mechanisms, in order to alleviate the salt-induced injury. Furthermore, Na+ extrusion to apoplast does not appear to be an efficient strategy for salt tolerance in pepper plants. PMID:25429292

  5. Nucleolus: the fascinating nuclear body

    PubMed Central

    Sirri, Valentina; Urcuqui-Inchima, Silvio; Roussel, Pascal

    2007-01-01

    Nucleoli are the prominent contrasted structures of the cell nucleus. In the nucleolus, ribosomal RNAs are synthesized, processed and assembled with ribosomal proteins. RNA polymerase I synthesizes the ribosomal RNAs and this activity is cell cycle regulated. The nucleolus reveals the functional organization of the nucleus in which the compartmentation of the different steps of ribosome biogenesis is observed whereas the nucleolar machineries are in permanent exchange with the nucleoplasm and other nuclear bodies. After mitosis, nucleolar assembly is a time and space regulated process controlled by the cell cycle. In addition, by generating a large volume in the nucleus with apparently no RNA polymerase II activity, the nucleolus creates a domain of retention/sequestration of molecules normally active outside the nucleolus. Viruses interact with the nucleolus and recruit nucleolar proteins to facilitate virus replication. The nucleolus is also a sensor of stress due to the redistribution of the ribosomal proteins in the nucleoplasm by nucleolus disruption. The nucleolus plays several crucial functions in the nucleus: in addition to its function as ribosome factory of the cells it is a multifunctional nuclear domain, and nucleolar activity is linked with several pathologies. Perspectives on the evolution of this research area are proposed. PMID:18046571

  6. Inhibition of Glutathione Biosynthesis Alters Compartmental Redox Status and the Thiol Proteome in Organogenesis-Stage Rat Conceptuses

    PubMed Central

    Harris, Craig; Shuster, Daniel Z.; Gomez, Rosaicela Roman; Sant, Karilyn E.; Reed, Matthew S.; Pohl, Jan; Hansen, Jason M.

    2013-01-01

    significant net oxidation was seen in the BSO-treated AF compartment after 6 hr. Biotinylated iodoacetamide (BIAM) labeling of proteins revealed the significant thiol-oxidation of many EMB proteins following BSO treatment. Quantitative changes in the thiol proteome, associated with developmentally-relevant pathways, were detected using isotope coded affinity tag (ICAT) labeling and mass spectroscopy. Adaptive pathways were selectively enriched with increased concentrations of proteins involved in mRNA processing (splicesome) and mRNA stabilization (glycolysis, GAPDH), as well as, protein synthesis (aminoacyl-tRNA) and protein folding (antigen processing, Hsp70, protein disulfide isomerase). These results show the ability of chemical and environmental modulators to selectively alter compartmental intracellular and extracellular GSH and Cys concentrations and change their corresponding Eh within the intact viable conceptus. The altered Eh were also of sufficient magnitude to alter the redox proteome and change relative protein concentrations suggesting that the mechanistic links through which environmental factors inform and regulate developmental signaling pathways may be discovered using systems developmental biology techniques. PMID:23736079

  7. Inhibition of glutathione biosynthesis alters compartmental redox status and the thiol proteome in organogenesis-stage rat conceptuses.

    PubMed

    Harris, Craig; Shuster, Daniel Z; Roman Gomez, Rosaicela; Sant, Karilyn E; Reed, Matthew S; Pohl, Jan; Hansen, Jason M

    2013-10-01

    oxidation was seen in the BSO-treated AF compartment after 6 h. Biotinylated iodoacetamide (BIAM) labeling of proteins revealed the significant thiol oxidation of many EMB proteins following BSO treatment. Quantitative changes in the thiol proteome, associated with developmentally relevant pathways, were detected using isotope coded affinity tag (ICAT) labeling and mass spectroscopy. Adaptive pathways were selectively enriched with increased concentrations of proteins involved in mRNA processing (splicesome) and mRNA stabilization (glycolysis, GAPDH), as well as protein synthesis (aminoacyl-tRNA) and protein folding (antigen processing, Hsp70, protein disulfide isomerase). These results show the ability of chemical and environmental modulators to selectively alter compartmental intracellular and extracellular GSH and Cys concentrations and change their corresponding E(h) within the intact viable conceptus. The altered E(h) were also of sufficient magnitude to alter the redox proteome and change relative protein concentrations, suggesting that the mechanistic links through which environmental factors inform and regulate developmental signaling pathways may be discovered using systems developmental biology techniques. PMID:23736079

  8. CFTR regulation in human airway epithelial cells requires integrity of the actin cytoskeleton and compartmentalized cAMP and PKA activity

    PubMed Central

    Monterisi, Stefania; Favia, Maria; Guerra, Lorenzo; Cardone, Rosa A.; Marzulli, Domenico; Reshkin, Stephan J.; Casavola, Valeria; Zaccolo, Manuela

    2012-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) mutation ΔF508CFTR still causes regulatory defects when rescued to the apical membrane, suggesting that the intracellular milieu might affect its ability to respond to cAMP regulation. We recently reported that overexpression of the Na+/H+ exchanger regulatory factor NHERF1 in the cystic fibrosis (CF) airway cell line CFBE41o-rescues the functional expression of ΔF508CFTR by promoting F-actin organization and formation of the NHERF1–ezrin–actin complex. Here, using real-time FRET reporters of both PKA activity and cAMP levels, we find that lack of an organized subcortical cytoskeleton in CFBE41o-cells causes both defective accumulation of cAMP in the subcortical compartment and excessive cytosolic accumulation of cAMP. This results in reduced subcortical levels and increased cytosolic levels of PKA activity. NHERF1 overexpression in CFBE41o-cells restores chloride secretion, subcortical cAMP compartmentalization and local PKA activity, indicating that regulation of ΔF508CFTR function requires not only stable expression of the mutant CFTR at the cell surface but also depends on both generation of local cAMP signals of adequate amplitude and activation of PKA in proximity of its target. Moreover, we found that the knockdown of wild-type CFTR in the non-CF 16HBE14o-cells results in both altered cytoskeletal organization and loss of cAMP compartmentalization, whereas stable overexpression of wt CFTR in CF cells restores cytoskeleton organization and re-establishes the compartmentalization of cAMP at the plasma membrane. This suggests that the presence of CFTR on the plasma membrane influences the cytoskeletal organizational state and, consequently, cAMP distribution. Our data show that a sufficiently high concentration of cAMP in the subcortical compartment is required to achieve PKA-mediated regulation of CFTR activity. PMID:22302988

  9. Nuclear power and nuclear weapons

    SciTech Connect

    Vaughen, V.C.A.

    1983-01-01

    The proliferation of nuclear weapons and the expanded use of nuclear energy for the production of electricity and other peaceful uses are compared. The difference in technologies associated with nuclear weapons and nuclear power plants are described.

  10. Development and Evaluation of a Compartmental Picture Archiving and Communications System Model for Integration and Visualization of Multidisciplinary Biomedical Data to Facilitate Student Learning in an Integrative Health Clinic

    ERIC Educational Resources Information Center

    Chow, Meyrick; Chan, Lawrence

    2010-01-01

    Information technology (IT) has the potential to improve the clinical learning environment. The extent to which IT enhances or detracts from healthcare professionals' role performance can be expected to affect both student learning and patient outcomes. This study evaluated nursing students' satisfaction with a novel compartmental Picture…

  11. Ivory Tower to Concrete Jungle Revisited

    ERIC Educational Resources Information Center

    Crebert, Gay; Bates, Merrelyn; Bell, Barry; Patrick, Carol-Joy; Cragnolini, Vanda

    2004-01-01

    In 2001-02, a project team at Griffith University undertook Stage 4 of the Griffith Graduate Project. Stage 4 used a survey and focus group discussions to gather graduates' and employers' perceptions of the role of the university, work placements and postgraduation employment in the development of generic skills and abilities. This article will…

  12. Tracking hippo in the cancer jungle.

    PubMed

    Suh, Jung H; Saba, Julie D

    2014-07-17

    Signaling through the Hippo pathway controls major aspects of cell growth and proliferation. Focusing on the metabolic consequences of Hippo signaling, Mulvihill and colleagues in this issue of Chemistry & Biology employ a large scale, integrative approach and uncover downstream reorganization of cellular metabolism when the effector TAZ is upregulated, identifying new connections to lipid metabolism. PMID:25036773

  13. From Answer Garden to Answer Jungle.

    ERIC Educational Resources Information Center

    Dron, Jon; Mitchell, Richard; Siviter, Phil

    1998-01-01

    The use of Usenet newsgroups in a computing and information systems classroom at the University of Brighton showed how Internet-based learning systems can encourage rapid evolution so that resources adapt to learners' needs. Although not always used as intended, and including off-topic distractions, newsgroups did accommodate learning styles and…

  14. Jungle in the heart of the city

    NASA Astrophysics Data System (ADS)

    Kolodziejska, Magdalena; Czerniak-Czyzniak, Marta

    2015-04-01

    Lessons of nature can be an interesting adventure for students if we allow them to actively participate in such activities. Students must engage in educational activities but thanks to them they also better absorb more knowledge and abilities. These types of activities also require proper preparation of the teacher, who should first get to know the area and next prepare a plan for the trip and also define objectives, tasks and issues that confront students. By providing such training for teachers, you can show various methods and forms of work, which allow to use the resources of the local environment. The area of the Vistula River is such an amazing place in Warsaw (capital of Poland). The phenomenon of this place is its wildness in the heart of the city. Fortunately, urbanization has not destroyed its wildness. Teachers are encouraged to use these unique resources in working with students. During the training they receive information and tools that help them to carry out such activities. Outdoor activities give possibility for cross subjects integration that is essential in modern teaching because in this place the content of different subjects complement each other. During these classes students gain not only the theoretical knowledge but also a comprehensive knowledge and intelligently learn the world around us and experience the processes occurring in the natural environment and cultural heritage. Interesting outdoor activities affect the growth of motivation of young people and affect their interest in natural subjects. During outdoor activities they observe the processes and phenomena in the natural place of their occurrence. Such activities can be treated both as providing the general overview for certain topics as well as its deepening. Students during an outdoor activity acquire abilities and improve practical skills. Also important is the ability to pursue educational goals. Observing the environment, students learn the culture of communing with nature. Outdoor activities shape students attitudes and beliefs about the need for rational management of natural resources and to join the efforts for nature and the environment. You cannot here omit the fact that the students often during communication with nature can establish strong emotional ties, he/she becomes sensitive to its beauty, also convinced of the need to protect the environment and most importantly can feel partly responsible for her condition. Outdoor activities engage all students to work and not just the most talented. It also allows for direct contact with the environment, offers the possibility of physical activity in the open air, allows for involvement of all sense receptors and thus are recognized by students, regardless of their age, for the most attractive. According to Piaget's theory "Thanks to activity in the external world a child (person) achieves the knowledge of the methods and regularities of its functioning". The author points out how important is to teach by an action especially when the student alone can experience the world around him/her.

  15. Pipeliners beat designers across Panama's jungle

    SciTech Connect

    Not Available

    1982-05-27

    Hard-driving pipeline crews are slashing a path down the steep slopes of the Andes range on Panama's Caribbean coast for the final leg of an 80-mile Pacific-Atlantic oil link that will reduce shipping times for North Slope crude to Gulf Coast refineries. When completed in late August, the trans-isthmus tube will be able to drain the Panama Canal of Alaskan oil, which currently must be pumped from large tankers to 65,000 ton ships before passage through the 50-mile cut. The 36 and 40-in.-dia pipe will connect an existing Northville oil transshipment terminal at Puerto Armuelles, near Costa Rica on the Pacific Coast, with a new 2.5-million-bbl storage area at Chiriqui Grande on the Caribbean coast. Two pumping stations, one at Puerto Armuelles and another at the base of the Serrania de Tabasara mountains, will lift the oil 4,000 ft over the Continental Divide. Gravity flows of 7 1/2 ft per second down the steep drop to the swamps along the Caribbean will feed three 833,000-bbl tanks being built on a hillside overlooking Chiriqui Bay. From there, two 36-in. lines will feed concrete-coated pipe sections trenched into the surf zone and placed on the muddy bottom for the remaining distance to two marine loading buoys over a mile offshore. The catenary anchor-leg mooring buoys are designed to handle tankers of up to 160,000 tons in 65 ft of water at maximum fill rates of 120,000 bbl per hour.

  16. Navigating Your Way through the Research Jungle

    ERIC Educational Resources Information Center

    Bauer, Scott; Brazer, David

    2012-01-01

    These days, information overload seems to be the normal state of existence. School leaders are inundated with descriptions of best practices and programs that work. They are exhorted to use evidence in all facets of decision-making and to employ research-based strategies to improve schools. Of course, research findings are seldom definitive, and…

  17. Celtic Tiger Found in Education Jungle

    ERIC Educational Resources Information Center

    Cooney, Thomas M.

    2008-01-01

    Purpose: While the growth of the Irish economy ("Celtic Tiger") has been well documented, not enough attention has been given to the role of education as a cornerstone for the success. This paper seeks to review education policy in Ireland over the past 50 years and to identify the significant educational initiatives that helped shape modern…

  18. Cooperative catalysis of noncompatible catalysts through compartmentalization: wacker oxidation and enzymatic reduction in a one-pot process in aqueous media.

    PubMed

    Sato, Hirofumi; Hummel, Werner; Gröger, Harald

    2015-04-01

    A Wacker oxidation using CuCl/PdCl2 as a catalyst system was successfully combined with an enzymatic ketone reduction to convert styrene enantioselectively into 1-phenylethanol in a one-pot process, although the two reactions conducted in aqueous media are not compatible due to enzyme deactivation by Cu ions. The one-pot feasibility was achieved via compartmentalization of the reactions. Conducting the Wacker oxidation in the interior of a polydimethylsiloxane thimble enables diffusion of only the organic substrate and product into the exterior where the biotransformation takes place. Thus, the Cu ions detrimental to the enzyme are withheld from the reaction media of the biotransformation. In this one-pot process, which formally corresponds to an asymmetric hydration of alkenes, a range of 1-arylethanols were formed with high conversions and 98-99 % ee. In addition, the catalyst system of the Wacker oxidation was recycled 15 times without significant decrease in conversion. PMID:25704961

  19. Synthesis, structural characterization and DFT calculation on a square-planar Ni(II) complex of a compartmental Schiff base ligand

    NASA Astrophysics Data System (ADS)

    Biswas, Surajit; Dolai, Malay; Dutta, Arpan; Ali, Mahammad

    2016-12-01

    Reaction of a symmetric compartmental Schiff-base ligand, (H2L) with nickel(II) perchlorate hexahydrate in 1:1 M ratio in methanol gives rise to a mononuclear nickel(II) compound, NiL (1). The compound has been characterized by C, H, N microanalyses and UV-Vis spectra. The single crystal X-ray diffraction studies reveal a square planar geometry around the Ni(II) center. The compound crystallizes in monoclinic system with space group C2/c with a = 21.6425(6), b = 9.9481(3), c = 13.1958(4) Å, β = 107.728(2)°, V = 2706.16(14) Å3 and Z = 4. Ground state DFT optimization and TDDFT calculations on the ligand and complex were performed to get their UV-Vis spectral pattern.

  20. Biodegradation of a mixture of the herbicides ametryn, and 2,4-dichlorophenoxyacetic acid (2,4-D) in a compartmentalized biofilm reactor.

    PubMed

    Sandoval-Carrasco, Carlos A; Ahuatzi-Chacón, Deifilia; Galíndez-Mayer, Juvencio; Ruiz-Ordaz, Nora; Juárez-Ramírez, Cleotilde; Martínez-Jerónimo, Fernando

    2013-10-01

    In this work, an efficient degradation process for the removal of 2,4-D and ametryn, together with organic and inorganic adjuvants used in the commercial formulations of both herbicides, was developed. Although both compounds are toxic for microbial communities, ametryn is markedly more toxic than 2,4-D. In spite of this, the microbial consortium used could resist loading rates up to 31.5 mg L(-1) d(-1) of ametryn, with removal efficiencies up to 97% for both herbicides. Thus, an alternative use of this consortium could be bioaugmentation, as a tool to protect the structure and function of an activated-sludge biota against ametryn or 2,4-D shock loads. The process was carried out in a lab-scale prototype of aerobic biobarrier constructed as a compartmentalized fixed film reactor with airlift recirculation of oxygenated liquid. PMID:23566464

  1. Effect of scatter correction on the compartmental measurement of striatal and extrastriatal dopamine D2 receptors using [123I]epidepride SPET.

    PubMed

    Fujita, Masahiro; Varrone, Andrea; Kim, Kyeong Min; Watabe, Hiroshi; Zoghbi, Sami S; Seneca, Nicholas; Tipre, Dnyanesh; Seibyl, John P; Innis, Robert B; Iida, Hidehiro

    2004-05-01

    Prior studies with anthropomorphic phantoms and single, static in vivo brain images have demonstrated that scatter correction significantly improves the accuracy of regional quantitation of single-photon emission tomography (SPET) brain images. Since the regional distribution of activity changes following a bolus injection of a typical neuroreceptor ligand, we examined the effect of scatter correction on the compartmental modeling of serial dynamic images of striatal and extrastriatal dopamine D(2) receptors using [(123)I]epidepride. Eight healthy human subjects [age 30+/-8 (range 22-46) years] participated in a study with a bolus injection of 373+/-12 (354-389) MBq [(123)I]epidepride and data acquisition over a period of 14 h. A transmission scan was obtained in each study for attenuation and scatter correction. Distribution volumes were calculated by means of compartmental nonlinear least-squares analysis using metabolite-corrected arterial input function and brain data processed with scatter correction using narrow-beam geometry micro (SC) and without scatter correction using broad-beam micro (NoSC). Effects of SC were markedly different among brain regions. SC increased activities in the putamen and thalamus after 1-1.5 h while it decreased activity during the entire experiment in the temporal cortex and cerebellum. Compared with NoSC, SC significantly increased specific distribution volume in the putamen (58%, P=0.0001) and thalamus (23%, P=0.0297). Compared with NoSC, SC made regional distribution of the specific distribution volume closer to that of [(18)F]fallypride. It is concluded that SC is required for accurate quantification of distribution volumes of receptor ligands in SPET studies. PMID:14730406

  2. Work-Related Pain in Extrinsic Finger Extensor Musculature of Instrumentalists Is Associated with Intracellular pH Compartmentation during Exercise

    PubMed Central

    Moreno-Torres, Angel; Rosset-Llobet, Jaume; Pujol, Jesus; Fàbregas, Sílvia; Gonzalez-de-Suso, Jose-Manuel

    2010-01-01

    Background Although non-specific pain in the upper limb muscles of workers engaged in mild repetitive tasks is a common occupational health problem, much is unknown about the associated structural and biochemical changes. In this study, we compared the muscle energy metabolism of the extrinsic finger extensor musculature in instrumentalists suffering from work-related pain with that of healthy control instrumentalists using non-invasive phosphorus magnetic resonance spectroscopy (31P-MRS). We hypothesize that the affected muscles will show alterations related with an impaired energy metabolism. Methodology/Principal Findings We studied 19 volunteer instrumentalists (11 subjects with work-related pain affecting the extrinsic finger extensor musculature and 8 healthy controls). We used 31P-MRS to find deviations from the expected metabolic response to exercise in phosphocreatine (PCr), inorganic phosphate (Pi), Pi/PCr ratio and intracellular pH kinetics. We observed a reduced finger extensor exercise tolerance in instrumentalists with myalgia, an intracellular pH compartmentation in the form of neutral and acid compartments, as detected by Pi peak splitting in 31P-MRS spectra, predominantly in myalgic muscles, and a strong association of this pattern with the condition. Conclusions/Significance Work-related pain in the finger extrinsic extensor muscles is associated with intracellular pH compartmentation during exercise, non-invasively detectable by 31P-MRS and consistent with the simultaneous energy production by oxidative metabolism and glycolysis. We speculate that a deficit in energy production by oxidative pathways may exist in the affected muscles. Two possible explanations for this would be the partial and/or local reduction of blood supply and the reduction of the muscle oxidative capacity itself. PMID:20161738

  3. Nuclear rights - nuclear wrongs

    SciTech Connect

    Paul, E.F.; Miller, F.D.; Paul, J.; Ahrens, J.

    1986-01-01

    This book contains 11 selections. The titles are: Three Ways to Kill Innocent Bystanders: Some Conundrums Concerning the Morality of War; The International Defense of Liberty; Two Concepts of Deterrence; Nuclear Deterrence and Arms Control; Ethical Issues for the 1980s; The Moral Status of Nuclear Deterrent Threats; Optimal Deterrence; Morality and Paradoxical Deterrence; Immoral Risks: A Deontological Critique of Nuclear Deterrence; No War Without Dictatorship, No Peace Without Democracy: Foreign Policy as Domestic Politics; Marxism-Leninism and its Strategic Implications for the United States; Tocqueveille War.

  4. Nuclear Medicine.

    ERIC Educational Resources Information Center

    Badawi, Ramsey D.

    2001-01-01

    Describes the use of nuclear medicine techniques in diagnosis and therapy. Describes instrumentation in diagnostic nuclear medicine and predicts future trends in nuclear medicine imaging technology. (Author/MM)

  5. Nuclear data for nuclear transmutation

    SciTech Connect

    Harada, Hideo

    2009-05-04

    Current status on nuclear data for the study of nuclear transmutation of radioactive wastes is reviewed, mainly focusing on neutron capture reactions. It is stressed that the highest-precision frontier research in nuclear data measurements should be a key to satisfy the target accuracies on the nuclear data requested for realizing the nuclear transmutation.

  6. Cause and Consequence of Tethering a SubTAD to Different Nuclear Compartments.

    PubMed

    Wijchers, Patrick J; Krijger, Peter H L; Geeven, Geert; Zhu, Yun; Denker, Annette; Verstegen, Marjon J A M; Valdes-Quezada, Christian; Vermeulen, Carlo; Janssen, Mark; Teunissen, Hans; Anink-Groenen, Lisette C M; Verschure, Pernette J; de Laat, Wouter

    2016-02-01

    Detailed genomic contact maps have revealed that chromosomes are structurally organized in megabase-sized topologically associated domains (TADs) that encompass smaller subTADs. These domains segregate in the nuclear space to form active and inactive nuclear compartments, but cause and consequence of compartmentalization are largely unknown. Here, we combined lacO/lacR binding platforms with allele-specific 4C technologies to track their precise position in the three-dimensional genome upon recruitment of NANOG, SUV39H1, or EZH2. We observed locked genomic loci resistant to spatial repositioning and unlocked loci that could be repositioned to different nuclear subcompartments with distinct chromatin signatures. Focal protein recruitment caused the entire subTAD, but not surrounding regions, to engage in new genomic contacts. Compartment switching was found uncoupled from transcription changes, and the enzymatic modification of histones per se was insufficient for repositioning. Collectively, this suggests that trans-associated factors influence three-dimensional compartmentalization independent of their cis effect on local chromatin composition and activity. PMID:26833089

  7. Cause and Consequence of Tethering a SubTAD to Different Nuclear Compartments

    PubMed Central

    Wijchers, Patrick J.; Krijger, Peter H.L.; Geeven, Geert; Zhu, Yun; Denker, Annette; Verstegen, Marjon J.A.M.; Valdes-Quezada, Christian; Vermeulen, Carlo; Janssen, Mark; Teunissen, Hans; Anink-Groenen, Lisette C.M.; Verschure, Pernette J.; de Laat, Wouter

    2016-01-01

    Summary Detailed genomic contact maps have revealed that chromosomes are structurally organized in megabase-sized topologically associated domains (TADs) that encompass smaller subTADs. These domains segregate in the nuclear space to form active and inactive nuclear compartments, but cause and consequence of compartmentalization are largely unknown. Here, we combined lacO/lacR binding platforms with allele-specific 4C technologies to track their precise position in the three-dimensional genome upon recruitment of NANOG, SUV39H1, or EZH2. We observed locked genomic loci resistant to spatial repositioning and unlocked loci that could be repositioned to different nuclear subcompartments with distinct chromatin signatures. Focal protein recruitment caused the entire subTAD, but not surrounding regions, to engage in new genomic contacts. Compartment switching was found uncoupled from transcription changes, and the enzymatic modification of histones per se was insufficient for repositioning. Collectively, this suggests that trans-associated factors influence three-dimensional compartmentalization independent of their cis effect on local chromatin composition and activity. PMID:26833089

  8. Nuclear weapons and nuclear war

    SciTech Connect

    Cassel, C.; McCally, M.; Abraham, H.

    1984-01-01

    This book examines the potential radiation hazards and environmental impacts of nuclear weapons. Topics considered include medical responsibility and thermonuclear war, the threat of nuclear war, nuclear weaponry, biological effects, radiation injury, decontamination, long-term effects, ecological effects, psychological aspects, the economic implications of nuclear weapons and war, ethics, civil defense, arms control, nuclear winter, and long-term biological consequences of nuclear war.

  9. Cytoplasmic localization of Hug1p, a negative regulator of the MEC1 pathway, coincides with the compartmentalization of Rnr2p–Rnr4p

    SciTech Connect

    Ainsworth, William B.; Hughes, Bridget Todd; Au, Wei Chun; Sakelaris, Sally; Kerscher, Oliver; Benton, Michael G.; Basrai, Munira A.

    2013-10-04

    Highlights: •Hug1p overexpression sensitizes wild-type cells to DNA damage and hydroxyurea (HU). •Expression of Hug1p in response to HU treatment is delayed relative to Rnr3p. •MEC1 pathway genes are required for cytoplasmic localization of Hug1p. •Hug1p subcellular compartmentalization to the cytoplasm coincides with Rnr2p–Rnr4p. -- Abstract: The evolutionarily conserved MEC1 checkpoint pathway mediates cell cycle arrest and induction of genes including the RNR (Ribonucleotide reductase) genes and HUG1 (Hydroxyurea, ultraviolet, and gamma radiation) in response to DNA damage and replication arrest. Rnr complex activity is in part controlled by cytoplasmic localization of the Rnr2p–Rnr4p subunits and inactivation of negative regulators Sml1p and Dif1p upon DNA damage and hydroxyurea (HU) treatment. We previously showed that a deletion of HUG1 rescues lethality of mec1Δ and suppresses dun1Δ strains. In this study, multiple approaches demonstrate the regulatory response of Hug1p to DNA damage and HU treatment and support its role as a negative effector of the MEC1 pathway. Consistent with our hypothesis, wild-type cells are sensitive to DNA damage and HU when HUG1 is overexpressed. A Hug1 polyclonal antiserum reveals that HUG1 encodes a protein in budding yeast and its MEC1-dependent expression is delayed compared to the rapid induction of Rnr3p in response to HU treatment. Cell biology and subcellular fractionation experiments show localization of Hug1p-GFP to the cytoplasm upon HU treatment. The cytoplasmic localization of Hug1p-GFP is dependent on MEC1 pathway genes and coincides with the cytoplasmic localization of Rnr2p–Rnr4p. Taken together, the genetic interactions, gene expression, and localization studies support a novel role for Hug1p as a negative regulator of the MEC1 checkpoint response through its compartmentalization with Rnr2p–Rnr4p.

  10. Nuclear Matrix protein SMAR1 represses HIV-1 LTR mediated transcription through chromatin remodeling

    SciTech Connect

    Sreenath, Kadreppa; Pavithra, Lakshminarasimhan; Singh, Sandeep; Sinha, Surajit; Dash, Prasanta K.; Siddappa, Nagadenahalli B.; Ranga, Udaykumar; Mitra, Debashis; Chattopadhyay, Samit

    2010-04-25

    Nuclear Matrix and MARs have been implicated in the transcriptional regulation of host as well as viral genes but their precise role in HIV-1 transcription remains unclear. Here, we show that > 98% of HIV sequences contain consensus MAR element in their promoter. We show that SMAR1 binds to the LTR MAR and reinforces transcriptional silencing by tethering the LTR MAR to nuclear matrix. SMAR1 associated HDAC1-mSin3 corepressor complex is dislodged from the LTR upon cellular activation by PMA/TNFalpha leading to an increase in the acetylation and a reduction in the trimethylation of histones, associated with the recruitment of RNA Polymerase II on the LTR. Overexpression of SMAR1 lead to reduction in LTR mediated transcription, both in a Tat dependent and independent manner, resulting in a decreased virion production. These results demonstrate the role of SMAR1 in regulating viral transcription by alternative compartmentalization of LTR between the nuclear matrix and chromatin.

  11. Phagosomes induced by cytokines function as anti-Listeria vaccines: novel role for functional compartmentalization of STAT-1 protein and cathepsin-D.

    PubMed

    Carrasco-Marín, Eugenio; Rodriguez-Del Rio, Estela; Frande-Cabanes, Elisabet; Tobes, Raquel; Pareja, Eduardo; Lecea-Cuello, M Jesús; Ruiz-Sáez, Marta; Madrazo-Toca, Fidel; Hölscher, Christoph; Alvarez-Dominguez, Carmen

    2012-04-27

    Phagosomes are critical compartments for innate immunity. However, their role in the protection against murine listeriosis has not been examined. We describe here that listericidal phago-receptosomes are induced by the function of IFN-γ or IL-6 as centralized compartments for innate and adaptive immunity because they are able to confer protection against murine listeriosis. These phago-receptosomes elicited LLO(91-99)/CD8(+)- and LLO(189-201)/CD4(+)-specific immune responses and recruited mature dendritic cells to the vaccination sites controlled by T cells. Moreover, they present exceptional features as efficient vaccine vectors. First, they compartmentalize a novel listericidal STAT-1-mediated signaling pathway that confines multiple innate immune components to the same environment. Second, they show features of MHC class II antigen-loading competent compartments for cathepsin-D-mediated LLO processing. Third, murine cathepsin-D deficiencies fail to develop protective immunity after vaccination with listericidal phago-receptosomes induced by IFN-γ or IL-6. Therefore, it appears that the connection of STAT-1 and cathepsin-D in a single compartment is relevant for protection against listeriosis. PMID:22337873

  12. Compartmentation of Metabolism of the C12-, C9-, and C5-n-dicarboxylates in Rat Liver, Investigated by Mass Isotopomer Analysis

    PubMed Central

    Jin, Zhicheng; Bian, Fang; Tomcik, Kristyen; Kelleher, Joanne K.; Zhang, Guo-Fang; Brunengraber, Henri

    2015-01-01

    We investigated the compartmentation of the catabolism of dodecanedioate (DODA), azelate, and glutarate in perfused rat livers, using a combination of metabolomics and mass isotopomer analyses. Livers were perfused with recirculating or nonrecirculating buffer containing one fully 13C-labeled dicarboxylate. Information on the peroxisomal versus mitochondrial catabolism was gathered from the labeling patterns of acetyl-CoA proxies, i.e. total acetyl-CoA, the acetyl moiety of citrate, C-1 + 2 of β-hydroxybutyrate, malonyl-CoA, and acetylcarnitine. Additional information was obtained from the labeling patterns of citric acid cycle intermediates and related compounds. The data characterize the partial oxidation of DODA and azelate in peroxisomes, with terminal oxidation in mitochondria. We did not find evidence of peroxisomal oxidation of glutarate. Unexpectedly, DODA contributes a substantial fraction to anaplerosis of the citric acid cycle. This opens the possibility to use water-soluble DODA in nutritional or pharmacological anaplerotic therapy when other anaplerotic substrates are impractical or contraindicated, e.g. in propionic acidemia and methylmalonic acidemia. PMID:26070565

  13. The Early Expression of HLA-DR and CD64 Myeloid Markers Is Specifically Compartmentalized in the Blood and Lungs of Patients with Septic Shock

    PubMed Central

    Mikaszewska-Sokolewicz, Małgorzata; Hoser, Grażyna; Zielińska-Borkowska, Urszula

    2016-01-01

    Identification of reliable biomarkers is key to guide targeted therapies in septic patients. Expression monitoring of monocyte HLA-DR and neutrophil CD64 could fulfill the above need. However, it is unknown whether their expression on circulating cells reflects the status of tissue resident cells. We compared expressions of HLA-DR and CD64 markers in the circulation and airways of septic shock patients and evaluated their outcome prognostic value. The expression of CD64 on neutrophils and HLA-DR on monocytes was analyzed in the peripheral blood and mini-bronchoalveolar lavage fluid cells by flow cytometry. Twenty-seven patients with septic shock were enrolled into the study. The fluorescence intensity of HLA-DR on circulating monocytes was 3.5-fold lower than on the pulmonary monocytes (p = 0.01). The expression of CD64 on circulating and airway neutrophils was similar (p = 0.47). Only the expression of CD64 on circulating neutrophils was higher in nonsurvivors versus survivors (2.8-fold; p = 0.031). Pulmonary monocytes display a higher level of HLA-DR activation compared to peripheral blood monocytes but the expression of neutrophil CD64 is similar on lung and circulating cells. Death in septic patients was effectively predicted by neutrophil CD64 but not monocytic HLA-DR. Prognostic value of cellular activation markers in septic shock appears to strongly depend on their level of compartmentalization. PMID:27413252

  14. Building America Case Study: Apartment Compartmentalization with an Aerosol-Based Sealing Process - Queens, NY; Technology Solutions for New and Existing Homes, Energy Efficiency & Renewable Energy (EERE)

    SciTech Connect

    2015-07-01

    Air sealing of building enclosures is a difficult and time-consuming process. Current methods in new construction require laborers to physically locate small and sometimes large holes in multiple assemblies and then manually seal each of them. The innovation demonstrated under this research study was the automated air sealing and compartmentalization of buildings through the use of an aerosolized sealant, developed by the Western Cooling Efficiency Center at University of California Davis.
    CARB sought to demonstrate this new technology application in a multifamily building in Queens, NY. The effectiveness of the sealing process was evaluated by three methods: air leakage testing of overall apartment before and after sealing, point-source testing of individual leaks, and pressure measurements in the walls of the target apartment during sealing. Aerosolized sealing was successful by several measures in this study. Many individual leaks that are labor-intensive to address separately were well sealed by the aerosol particles. In addition, many diffuse leaks that are difficult to identify and treat were also sealed. The aerosol-based sealing process resulted in an average reduction of 71% in air leakage across three apartments and an average apartment airtightness of 0.08 CFM50/SF of enclosure area.

  15. In vitro digestion of short-dough biscuits enriched in proteins and/or fibres, using a multi-compartmental and dynamic system (1): viscosity measurement and prediction.

    PubMed

    Villemejane, C; Wahl, R; Aymard, P; Denis, S; Michon, C

    2015-09-01

    The effects of biscuit composition on the viscosity generated during digestion were investigated. A control biscuit, one with proteins, one with fibres, and one with both proteins and fibres were digested under the same conditions, using the TNO intestinal model (TIM-1). The TIM-1 is a multi-compartmental and dynamic in vitro system, simulating digestion in the upper tract (stomach and small intestine) of healthy adult humans. Digesta were collected at different times, in the different compartments of the TIM-1 (stomach, duodenum, jejunum and ileum) and viscosity was measured with a dynamic rheometer. Results showed a marked effect of biscuit composition on chyme viscosity. Highest viscosity was obtained with biscuits containing viscous soluble fibres, followed by those enriched in both proteins and fibres, then by protein-enriched and control biscuits. The viscosity was maintained throughout the gut up to the ileal compartment. A prediction of the evolution of the chyme viscosity in each compartment of the TIM-1 was built, based on model curves describing the evolution of the viscosity as a function of biscuit concentration, and on dilution factors measured by spectrophotometry on a blank digestion. PMID:25842308

  16. In vitro digestion of short-dough biscuits enriched in proteins and/or fibres using a multi-compartmental and dynamic system (2): Protein and starch hydrolyses.

    PubMed

    Villemejane, C; Denis, S; Marsset-Baglieri, A; Alric, M; Aymard, P; Michon, C

    2016-01-01

    The influence of protein and/or fibre enrichment on the nutritional properties of biscuits was studied in terms of proteolysis and amylolysis. Biscuits were digested using a multi-compartmental and dynamic system that simulates the main physiological digestive functions of the upper tract of healthy adult humans: the TIM-1. A control biscuit and three biscuits enriched in proteins and/or fibres were digested under the same conditions. Samples were collected in each compartment of the TIM-1 (stomach, duodenum, jejunum and ileum) at different times of digestion and analysed in terms of proteolysis and amylolysis. Results indicate that both formulation and processing impacted the digestive fate of the biscuits. Incorporating proteins or fibres in biscuits lowered or delayed proteolysis. Moreover a protein-plus-fibre additional or synergic effect was observed. Biscuits enriched in proteins and/or fibres displayed a higher amylolysis degree than the control biscuit, probably due to lower starch amounts and higher gelatinization degrees. PMID:26212956

  17. Compartmentation of Metabolism of the C12-, C9-, and C5-n-dicarboxylates in Rat Liver, Investigated by Mass Isotopomer Analysis: ANAPLEROSIS FROM DODECANEDIOATE.

    PubMed

    Jin, Zhicheng; Bian, Fang; Tomcik, Kristyen; Kelleher, Joanne K; Zhang, Guo-Fang; Brunengraber, Henri

    2015-07-24

    We investigated the compartmentation of the catabolism of dodecanedioate (DODA), azelate, and glutarate in perfused rat livers, using a combination of metabolomics and mass isotopomer analyses. Livers were perfused with recirculating or nonrecirculating buffer containing one fully (13)C-labeled dicarboxylate. Information on the peroxisomal versus mitochondrial catabolism was gathered from the labeling patterns of acetyl-CoA proxies, i.e. total acetyl-CoA, the acetyl moiety of citrate, C-1 + 2 of β-hydroxybutyrate, malonyl-CoA, and acetylcarnitine. Additional information was obtained from the labeling patterns of citric acid cycle intermediates and related compounds. The data characterize the partial oxidation of DODA and azelate in peroxisomes, with terminal oxidation in mitochondria. We did not find evidence of peroxisomal oxidation of glutarate. Unexpectedly, DODA contributes a substantial fraction to anaplerosis of the citric acid cycle. This opens the possibility to use water-soluble DODA in nutritional or pharmacological anaplerotic therapy when other anaplerotic substrates are impractical or contraindicated, e.g. in propionic acidemia and methylmalonic acidemia. PMID:26070565

  18. Genetic characterization of human immunodeficiency virus type 1 in blood and genital secretions: evidence for viral compartmentalization and selection during sexual transmission.

    PubMed Central

    Zhu, T; Wang, N; Carr, A; Nam, D S; Moor-Jankowski, R; Cooper, D A; Ho, D D

    1996-01-01

    To explore the mechanism of sexual transmission of human immunodeficiency virus type 1 (HIV-1), we compared HIV-1 gp120 sequences in longitudinal samples from five acute seroconvertors with those from their corresponding sexual partners (transmitters). We used a quantitative homoduplex tracking assay to compare the overall genetic composition of HIV-1 quasispecies in each transmission pair and to track the transmitted viruses during the acute and asymptomatic stages of HIV-1 infection. In the chronically infected transmitters, HIV-1 variants in genital secretions differed from those in blood and variants in cells differed from those in cell-free plasma, indicating remarkable sequence heterogeneity in these subjects as well as compartmentalization of the virus in different bodily sites. Conversely, two of five seroconvertors had only a few related variants and three of five harbored only one viral population, indicating that in these subjects the transmitted viruses were typically homogeneous. Transmitted viruses were evident in the donor's seminal plasma (one of five cases) and even more so in their seminal cells (three of five cases), suggesting that both cell-associated and cell-free viruses can be transmitted. In every pair studied, the transmitted variant(s) represents only a minor population in the semen of the corresponding transmitter, thereby providing evidence that HIV-1 selection indeed occurs during sexual transmission. PMID:8627789

  19. Gap Junctions as Common Cause of High-Frequency Oscillations and Epileptic Seizures in a Computational Cascade of Neuronal Mass and Compartmental Modeling.

    PubMed

    Helling, Robert M; Koppert, Marc M J; Visser, Gerhard H; Kalitzin, Stiliyan N

    2015-09-01

    High frequency oscillations (HFO) appear to be a promising marker for delineating the seizure onset zone (SOZ) in patients with localization related epilepsy. It remains, however, a purely observational phenomenon and no common mechanism has been proposed to relate HFOs and seizure generation. In this work we show that a cascade of two computational models, one on detailed compartmental scale and a second one on neural mass scale can explain both the autonomous generation of HFOs and the presence of epileptic seizures as emergent properties. To this end we introduce axonal-axonal gap junctions on a microscopic level and explore their impact on the higher level neural mass model (NMM). We show that the addition of gap junctions can generate HFOs and simultaneously shift the operational point of the NMM from a steady state network into bistable behavior that can autonomously generate epileptic seizures. The epileptic properties of the system, or the probability to generate epileptic type of activity, increases gradually with the increase of the density of axonal-axonal gap junctions. We further demonstrate that ad hoc HFO detectors used in previous studies are applicable to our simulated data. PMID:26058401

  20. Transcriptomic analysis of Streptomyces coelicolor differentiation in solid sporulating cultures: first compartmentalized and second multinucleated mycelia have different and distinctive transcriptomes.

    PubMed

    Yagüe, Paula; Rodríguez-García, Antonio; López-García, María T; Martín, Juan F; Rioseras, Beatriz; Sánchez, Jesús; Manteca, Angel

    2013-01-01

    Streptomycetes are very important industrial bacteria, which produce two thirds of all clinically relevant secondary metabolites. They have a complex developmental-cycle in which an early compartmentalized mycelium (MI) differentiates to a multinucleated mycelium (MII) that grows inside the culture medium (substrate mycelium) until it starts to growth into the air (aerial mycelium) and ends up forming spores. Streptomyces developmental studies have focused mainly on the later stages of MII differentiation (aerial mycelium and sporulation), with regulation of pre-sporulation stages (MI/MII transition) essentially unknown. This work represents the first study of the Streptomyces MI transcriptome, analyzing how it differs from the MII transcriptome. We have used a very conservative experimental approach to fractionate MI from MII and quantify gene expressions. The expression of well characterized key developmental/metabolic genes involved in bioactive compound production (actinorhodin, undecylprodigiosin, calcium-dependent antibiotic, cpk, geosmin) or hydrophobic cover formation-sporulation (bld, whi, wbl, rdl, chp, ram) was correlated with MII differentiation. Additionally, 122 genes conserved in the Streptomyces genus, whose biological function had not been previously characterized, were found to be differentially expressed (more than 4-fold) in MI or MII. These genes encoded for putative regulatory proteins (transcriptional regulators, kinases), as well as hypothetical proteins. Knowledge about differences between the MI (vegetative) and MII (reproductive) transcriptomes represents a huge advance in Streptomyces biology that will make future experiments possible aimed at characterizing the biochemical pathways controlling pre-sporulation developmental stages and activation of secondary metabolism in Streptomyces. PMID:23555999

  1. Unique mononuclear Mn(II) complexes of an end-off compartmental Schiff base ligand: experimental and theoretical studies on their bio-relevant catalytic promiscuity.

    PubMed

    Adhikary, Jaydeep; Chakraborty, Aratrika; Dasgupta, Sanchari; Chattopadhyay, Shyamal Kumar; Kruszynski, Rafał; Trzesowska-Kruszynska, Agata; Stepanović, Stepan; Gruden-Pavlović, Maja; Swart, Marcel; Das, Debasis

    2016-08-01

    Three new mononuclear manganese(ii) complexes, namely [Mn(HL)2]·2ClO4 (1), [Mn(HL)(N(CN)2)(H2O)2]·ClO4 (2) and [Mn(HL)(SCN)2] (3) [LH = 4-tert-butyl-2,6-bis-[(2-pyridin-2-yl-ethylimino)-methyl]-phenol], have been synthesized and structurally characterized. An "end-off" compartmental ligand (LH) possesses two symmetrical compartments with N2O binding sites but accommodates only one manganese atom instead of two due to the protonation of the imine nitrogen of one compartment. Although all three complexes are mononuclear, complex 1 is unique as it has a 1 : 2 metal to ligand stoichiometry. The catalytic promiscuity of complexes 1-3 in terms of two different bio-relevant catalytic activities namely catecholase and phenoxazinone synthase has been thoroughly investigated. EPR and cyclic voltametric studies reveal that radical formation rather than metal centered redox participation is responsible for their catecholase-like and phenoxazinone synthase-like catalytic activity. A computational approach suggests that imine bond bound radical generation rather than phenoxo radical formation is most likely responsible for the oxidizing properties of the complexes. PMID:27430642

  2. Compartmentalized and contrasted response of ectomycorrhizal and soil fungal communities of Scots pine forests along elevation gradients in France and Spain.

    PubMed

    Rincón, Ana; Santamaría-Pérez, Blanca; Rabasa, Sonia G; Coince, Aurore; Marçais, Benoit; Buée, Marc

    2015-08-01

    Fungi are principal actors of forest soils implied in many ecosystem services and the mediation of tree's responses. Forecasting fungal responses to environmental changes is necessary for maintaining forest productivity, although our partial understanding of how abiotic and biotic factors affect fungal communities is restricting the predictions. We examined fungal communities of Pinus sylvestris along elevation gradients to check potential responses to climate change-associated factors. Fungi of roots and soils were analysed at a regional scale, by using a high-throughput sequencing approach. Overall soil fungal richness increased with pH, whereas it did not vary with climate. However, when representative sub-assemblages, i.e. Ascomycetes/Basidiomycetes, and families were analysed, they differentially answered to climatic and edaphic variables. This response was dependent on where they settled, i.e. soil versus roots, and/or on their lifestyle, i.e. mycorrhizal or not, suggesting different potential functional weights within the community. Our results revealed a highly compartmentalized and contrasted response of fungal communities in forest soils. The different response of fungal sub-assemblages indicated a range of possible selective direct and indirect (i.e. via host) impacts of climatic variations on these communities, of unknown functional consequences, that helps in understanding potential fungal responses under future global change scenarios. PMID:25953485

  3. Transcriptomic Analysis of Streptomyces coelicolor Differentiation in Solid Sporulating Cultures: First Compartmentalized and Second Multinucleated Mycelia Have Different and Distinctive Transcriptomes

    PubMed Central

    Yagüe, Paula; Rodríguez-García, Antonio; López-García, María T.; Martín, Juan F.; Rioseras, Beatriz; Sánchez, Jesús; Manteca, Angel

    2013-01-01

    Streptomycetes are very important industrial bacteria, which produce two thirds of all clinically relevant secondary metabolites. They have a complex developmental-cycle in which an early compartmentalized mycelium (MI) differentiates to a multinucleated mycelium (MII) that grows inside the culture medium (substrate mycelium) until it starts to growth into the air (aerial mycelium) and ends up forming spores. Streptomyces developmental studies have focused mainly on the later stages of MII differentiation (aerial mycelium and sporulation), with regulation of pre-sporulation stages (MI/MII transition) essentially unknown. This work represents the first study of the Streptomyces MI transcriptome, analyzing how it differs from the MII transcriptome. We have used a very conservative experimental approach to fractionate MI from MII and quantify gene expressions. The expression of well characterized key developmental/metabolic genes involved in bioactive compound production (actinorhodin, undecylprodigiosin, calcium-dependent antibiotic, cpk, geosmin) or hydrophobic cover formation-sporulation (bld, whi, wbl, rdl, chp, ram) was correlated with MII differentiation. Additionally, 122 genes conserved in the Streptomyces genus, whose biological function had not been previously characterized, were found to be differentially expressed (more than 4-fold) in MI or MII. These genes encoded for putative regulatory proteins (transcriptional regulators, kinases), as well as hypothetical proteins. Knowledge about differences between the MI (vegetative) and MII (reproductive) transcriptomes represents a huge advance in Streptomyces biology that will make future experiments possible aimed at characterizing the biochemical pathways controlling pre-sporulation developmental stages and activation of secondary metabolism in Streptomyces. PMID:23555999

  4. Development of a paediatric population pharmacokinetic model for valacyclovir from literature non-compartmental values originating from sparse studies and Bayesian priors: a simulation study.

    PubMed

    Kechagia, Irene-Ariadne; Dokoumetzidis, Aristides

    2015-06-01

    A preliminary population pharmacokinetic (PopPK) model of valacyclovir in children was developed from non-compartmental analysis (NCA) parameter values from literature, including several age groups, combined with Bayesian priors from a PopPK model of acyclovir, the active metabolite of valacyclovir, from literature too. Also a simulation study was carried out to evaluate the performance of various modelling choices related to the estimation of model parameters from NCA parameters originating from sparse PK studies. Assuming a one-compartment model with first order absorption, a mixed effects, meta-analysis approach was utilized which allows accounting the random intergroup variability, the detection of covariates and the application of informative Bayesian priors on the parameters. The conclusions from the simulation study calculating bias and precision for various cases, were that a model which takes explicitly into account the sampling schedule, performs better than a model using the theoretical expressions of calculating the NCA parameters. Also by using the geometric rather than the arithmetic means of NCA parameters, less biased results are obtained. These findings guided the choices for the valacyclovir model, for which informative priors from a PopPK model of acyclovir were applied for some of the parameters, in order to include a richer covariate model for clearance, not supported by the NCA dataset and a value for bioavailability. This preliminary valacyclovir model can be used in simulations to provide dosage recommendations for children of various ages and to help design more efficiently prospective clinical trials. PMID:25821006

  5. Compartmental analysis of washout effect in rat brain: in-beam OpenPET measurement using a 11C beam

    NASA Astrophysics Data System (ADS)

    Hirano, Yoshiyuki; Kinouchi, Shoko; Ikoma, Yoko; Yoshida, Eiji; Wakizaka, Hidekazu; Ito, Hiroshi; Yamaya, Taiga

    2013-12-01

    In-beam positron emission tomography (PET) is expected to enable visualization of a dose verification using positron emitters (β+ decay). For accurate dose verification, correction of the washout of the positron emitters should be made. In addition, the quantitative washout rate has a potential usefulness as a diagnostic index, but modeling for this has not been studied yet. In this paper, therefore, we applied compartment analyses to in-beam PET data acquired by our small OpenPET prototype, which has a physically opened field-of-view (FOV) between two detector rings. A rat brain was located at the FOV and was irradiated by a 11C beam. Time activity curves of the irradiated field were measured immediately after the irradiations, and the washout rate was obtained based on two models: the two-washout model (medium decay, k2m; slow decay, k2s) developed in a study of rabbit irradiation; and the two-compartment model used in nuclear medicine, where efflux from tissue to blood (k2), influx (k3) and efflux (k4) from the first to second compartments in tissue were evaluated. The observed k2m and k2s were 0.34 and 0.005 min-1, respectively, which was consistent with the rabbit study. Also k2m was close to the washout rate in cerebral blood flow (CBF) measurements by dynamic PET with 15O-water, while, k2, k3, and k4 were 0.16, 0.15 and 0.007 min-1. Our present work suggested the dynamics of 11C might be relevant to CBF or permeability of a molecule containing 11C atoms might be regulated by a transporter because the k2 was relatively low compared with a simple diffusion tracer.

  6. Nuclear Scans

    MedlinePlus

    Nuclear scans use radioactive substances to see structures and functions inside your body. They use a special ... images. Most scans take 20 to 45 minutes. Nuclear scans can help doctors diagnose many conditions, including ...

  7. Nuclear Chemistry.

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1979

    1979-01-01

    Provides a brief review of the latest developments in nuclear chemistry. Nuclear research today is directed toward increased activity in radiopharmaceuticals and formation of new isotopes by high-energy, heavy-ion collisions. (Author/BB)

  8. Nuclear Winter.

    ERIC Educational Resources Information Center

    Ehrlich, Anne

    1984-01-01

    "Nuclear Winter" was recently coined to describe the climatic and biological effects of a nuclear war. These effects are discussed based on models, simulations, scenarios, and projections. Effects on human populations are also considered. (JN)

  9. Nuclear Fuels.

    ERIC Educational Resources Information Center

    Nash, J. Thomas

    1983-01-01

    Trends in and factors related to the nuclear industry and nuclear fuel production are discussed. Topics addressed include nuclear reactors, survival of the U.S. uranium industry, production costs, budget cuts by the Department of Energy and U.S. Geological survey for resource studies, mining, and research/development activities. (JN)

  10. Nuclear weapons, nuclear effects, nuclear war

    SciTech Connect

    Bing, G.F.

    1991-08-20

    This paper provides a brief and mostly non-technical description of the militarily important features of nuclear weapons, of the physical phenomena associated with individual explosions, and of the expected or possible results of the use of many weapons in a nuclear war. Most emphasis is on the effects of so-called ``strategic exchanges.``

  11. New quantitative approaches reveal the spatial preference of nuclear compartments in mammalian fibroblasts.

    PubMed

    Weston, David J; Russell, Richard A; Batty, Elizabeth; Jensen, Kirsten; Stephens, David A; Adams, Niall M; Freemont, Paul S

    2015-03-01

    The nuclei of higher eukaryotic cells display compartmentalization and certain nuclear compartments have been shown to follow a degree of spatial organization. To date, the study of nuclear organization has often involved simple quantitative procedures that struggle with both the irregularity of the nuclear boundary and the problem of handling replicate images. Such studies typically focus on inter-object distance, rather than spatial location within the nucleus. The concern of this paper is the spatial preference of nuclear compartments, for which we have developed statistical tools to quantitatively study and explore nuclear organization. These tools combine replicate images to generate 'aggregate maps' which represent the spatial preferences of nuclear compartments. We present two examples of different compartments in mammalian fibroblasts (WI-38 and MRC-5) that demonstrate new knowledge of spatial preference within the cell nucleus. Specifically, the spatial preference of RNA polymerase II is preserved across normal and immortalized cells, whereas PML nuclear bodies exhibit a change in spatial preference from avoiding the centre in normal cells to exhibiting a preference for the centre in immortalized cells. In addition, we show that SC35 splicing speckles are excluded from the nuclear boundary and localize throughout the nucleoplasm and in the interchromatin space in non-transformed WI-38 cells. This new methodology is thus able to reveal the effect of large-scale perturbation on spatial architecture and preferences that would not be obvious from single cell imaging. PMID:25631564

  12. New quantitative approaches reveal the spatial preference of nuclear compartments in mammalian fibroblasts

    PubMed Central

    Weston, David J.; Russell, Richard A.; Batty, Elizabeth; Jensen, Kirsten; Stephens, David A.; Adams, Niall M.; Freemont, Paul S.

    2015-01-01

    The nuclei of higher eukaryotic cells display compartmentalization and certain nuclear compartments have been shown to follow a degree of spatial organization. To date, the study of nuclear organization has often involved simple quantitative procedures that struggle with both the irregularity of the nuclear boundary and the problem of handling replicate images. Such studies typically focus on inter-object distance, rather than spatial location within the nucleus. The concern of this paper is the spatial preference of nuclear compartments, for which we have developed statistical tools to quantitatively study and explore nuclear organization. These tools combine replicate images to generate ‘aggregate maps' which represent the spatial preferences of nuclear compartments. We present two examples of different compartments in mammalian fibroblasts (WI-38 and MRC-5) that demonstrate new knowledge of spatial preference within the cell nucleus. Specifically, the spatial preference of RNA polymerase II is preserved across normal and immortalized cells, whereas PML nuclear bodies exhibit a change in spatial preference from avoiding the centre in normal cells to exhibiting a preference for the centre in immortalized cells. In addition, we show that SC35 splicing speckles are excluded from the nuclear boundary and localize throughout the nucleoplasm and in the interchromatin space in non-transformed WI-38 cells. This new methodology is thus able to reveal the effect of large-scale perturbation on spatial architecture and preferences that would not be obvious from single cell imaging. PMID:25631564

  13. Regulation of Sterol Content in Membranes by Subcellular Compartmentation of Steryl-Esters Accumulating in a Sterol-Overproducing Tobacco Mutant.

    PubMed Central

    Gondet, L.; Bronner, R.; Benveniste, P.

    1994-01-01

    The study of sterol overproduction in tissues of LAB 1-4 mutant tobacco (Nicotiana tabacum L. cv Xanthi) (P. Maillot-Vernier, H. Schaller, P. Benveniste, G. Belliard [1989] Biochem Biophys Res Commun 165: 125-130) over several generations showed that the overproduction phenotype is stable in calli, with a 10-fold stimulation of sterol content when compared with wild-type calli. However, leaves of LAB 1-4 plants obtained after two steps of self-fertilization were characterized by a mere 3-fold stimulation, whereas calli obtained from these plants retained a typical sterol-overproducing mutant phenotype (i.e. a 10-fold increase of sterol content). These results suggest that the expression of the LAB 1-4 phenotype is dependent on the differentiation state of cells. Most of the sterols accumulating in the mutant tissues were present as steryl-esters, which were minor species in wild-type tissues. Subcellular fractionation showed that in both mutant and wild-type tissues, free sterols were associated mainly with microsomal membranes. In contrast, the bulk of steryl-esters present in mutant tissues was found in the soluble fraction of cells. Numerous lipid droplets were detected in the hyaloplasm of LAB 1-4 cells by cytochemical and cytological techniques. After isolation, these lipid granules were shown to contain steryl-esters. These results show that the overproduced sterols of mutant tissues accumulate as steryl-esters in hyaloplasmic bodies. The esterification process thus allows regulation of the amount of free sterols in membranes by subcellular compartmentation. PMID:12232218

  14. Compartmentation Analysis of Paraquat Fluxes in Maize Roots as a Means of Estimating the Rate of Vacuolar Accumulation and Translocation to Shoots.

    PubMed Central

    DiTomaso, J. M.; Hart, J. J.; Kochian, L. V.

    1993-01-01

    Efflux analysis conducted after five loading periods of various lengths (2, 6, 12, 18, or 24 h) was used to investigate uptake, compartmentation, and translocation of [14C]paraquat in maize (Zea mays L.) seedlings. The time course for net paraquat uptake (paraquat concentration in uptake solution = 25[mu]M) into maize roots was linear (56.7 nmol g-1 root fresh weight h-1) for 24 h. Estimates of changes in paraquat content in the vacuole, cytoplasm, and cell wall after 2-, 6-, 12-, 18-, and 24-h loading periods indicated that the cell wall saturated rapidly, whereas accumulation of paraquat into the vacuole increased linearly (12.4 nmol g-1 root fresh weight h-1) over 24 h. In contrast to vacuolar accumulation, cytoplasmic paraquat content appeared to approach saturation. The half-time for paraquat efflux from the cell wall (16.6 min [plus or minus] 1.2 SD) and cytoplasm (58.8 min [plus or minus] 8.9 SD remained relatively constant regardless of the length of the loading period, whereas the half-time for efflux from the vacuole was considerably longer and increased linearly with increased loading time (6.1-18.7 h). The time course for paraquat translocation to the shoot was linear within a 24-h exposure to radiolabeled herbicide, but translocation did not begin until 5 h after initiation of treatment. The experimental approach used in these experiments provides a valuable method for examining the movement of paraquat in maize seedlings. Results indicate that the herbicide slowly accumulates in the vacuole of root cells but is also translocated to the shoot. PMID:12231834

  15. Resolving the Compartmentation and Function of C4 Photosynthesis in the Single-Cell C4 Species Bienertia sinuspersici1[OA

    PubMed Central

    Offermann, Sascha; Okita, Thomas W.; Edwards, Gerald E.

    2011-01-01

    Bienertia sinuspersici is a land plant known to perform C4 photosynthesis through the location of dimorphic chloroplasts in separate cytoplasmic domains within a single photosynthetic cell. A protocol was developed with isolated protoplasts to obtain peripheral chloroplasts (P-CP), a central compartment (CC), and chloroplasts from the CC (C-CP) to study the subcellular localization of photosynthetic functions. Analyses of these preparations established intracellular compartmentation of processes to support a NAD-malic enzyme (ME)-type C4 cycle. Western-blot analyses indicated that the CC has Rubisco from the C3 cycle, the C4 decarboxylase NAD-ME, a mitochondrial isoform of aspartate aminotransferase, and photorespiratory markers, while the C-CP and P-CP have high levels of Rubisco and pyruvate, Pidikinase, respectively. Other enzymes for supporting a NAD-ME cycle via an aspartate-alanine shuttle, carbonic anhydrase, phosophoenolpyruvate carboxylase, alanine, and an isoform of aspartate aminotransferase are localized in the cytosol. Functional characterization by photosynthetic oxygen evolution revealed that only the C-CP have a fully operational C3 cycle, while both chloroplast types have the capacity to photoreduce 3-phosphoglycerate. The P-CP were enriched in a putative pyruvate transporter and showed light-dependent conversion of pyruvate to phosphoenolpyruvate. There is a larger investment in chloroplasts in the central domain than in the peripheral domain (6-fold more chloroplasts and 4-fold more chlorophyll). The implications of this uneven distribution for the energetics of the C4 and C3 cycles are discussed. The results indicate that peripheral and central compartment chloroplasts in the single-cell C4 species B. sinuspersici function analogous to mesophyll and bundle sheath chloroplasts of Kranz-type C4 species. PMID:21263039

  16. A Compartmental Comparison of Major Lipid Species in a Coral-Symbiodinium Endosymbiosis: Evidence that the Coral Host Regulates Lipogenesis of Its Cytosolic Lipid Bodies.

    PubMed

    Chen, Hung-Kai; Song, Shin-Ni; Wang, Li-Hsueh; Mayfield, Anderson B; Chen, Yi-Jyun; Chen, Wan-Nan U; Chen, Chii-Shiarng

    2015-01-01

    The lipid body (LB) formation in the host coral gastrodermal cell cytoplasm is a hallmark of the coral-Symbiodinium endosymbiosis, and such lipid-based entities are not found in endosymbiont-free cnidarian cells. Therefore, the elucidation of lipogenesis regulation in LBs and how it is related to the lipid metabolism of the host and endosymbiont could provide direct insight to understand the symbiosis mechanism. Herein, the lipid composition of host cells of the stony coral Euphyllia glabrescens, as well as that of their cytoplasmic LBs and in hospite Symbiodinium populations, was examined by high performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS), and six major lipid species were identified: wax esters, sterol esters, triacylglycerols, cholesterols, free fatty acids, and phospholipids. Their concentrations differed significantly between host coral cells, LBs, and Symbiodinium, suggesting compartmental regulation. WE were only present in the host coral and were particularly highly concentrated in LBs. Amongst the four species of WE, the monoene R = C18:1/R = C16 was found to be LB-specific and was not present in the host gastrodermal cell cytoplasm. Furthermore, the acyl pool profiles of the individual LB lipid species were more similar, but not equal to, those of the host gastrodermal cells in which they were located, indicating partially autonomous lipid metabolism in these LBs. Nevertheless, given the overall similarity in the host gastrodermal cell and LB lipid profiles, these data suggest that a significant portion of the LB lipids may be of host coral origin. Finally, lipid profiles of the in hospite Symbiodinium populations were significantly distinct from those of the cultured Symbiodinium, potentially suggesting a host regulation effect that may be fundamental to lipid metabolism in endosymbiotic associations involving clade C Symbiodinium. PMID:26218797

  17. A Compartmental Comparison of Major Lipid Species in a Coral-Symbiodinium Endosymbiosis: Evidence that the Coral Host Regulates Lipogenesis of Its Cytosolic Lipid Bodies

    PubMed Central

    Chen, Hung-Kai; Song, Shin-Ni; Wang, Li-Hsueh; Mayfield, Anderson B.; Chen, Yi-Jyun; Chen, Wan-Nan U.; Chen, Chii-Shiarng

    2015-01-01

    The lipid body (LB) formation in the host coral gastrodermal cell cytoplasm is a hallmark of the coral-Symbiodinium endosymbiosis, and such lipid-based entities are not found in endosymbiont-free cnidarian cells. Therefore, the elucidation of lipogenesis regulation in LBs and how it is related to the lipid metabolism of the host and endosymbiont could provide direct insight to understand the symbiosis mechanism. Herein, the lipid composition of host cells of the stony coral Euphyllia glabrescens, as well as that of their cytoplasmic LBs and in hospite Symbiodinium populations, was examined by high performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS), and six major lipid species were identified: wax esters, sterol esters, triacylglycerols, cholesterols, free fatty acids, and phospholipids. Their concentrations differed significantly between host coral cells, LBs, and Symbiodinium, suggesting compartmental regulation. WE were only present in the host coral and were particularly highly concentrated in LBs. Amongst the four species of WE, the monoene R = C18:1/R = C16 was found to be LB-specific and was not present in the host gastrodermal cell cytoplasm. Furthermore, the acyl pool profiles of the individual LB lipid species were more similar, but not equal to, those of the host gastrodermal cells in which they were located, indicating partially autonomous lipid metabolism in these LBs. Nevertheless, given the overall similarity in the host gastrodermal cell and LB lipid profiles, these data suggest that a significant portion of the LB lipids may be of host coral origin. Finally, lipid profiles of the in hospite Symbiodinium populations were significantly distinct from those of the cultured Symbiodinium, potentially suggesting a host regulation effect that may be fundamental to lipid metabolism in endosymbiotic associations involving clade C Symbiodinium. PMID:26218797

  18. Synthesis, crystal structures and theoretical studies of dinuclear Mn(II) and Ni(II) complexes of phenol-based "end-off" compartmental ligand

    NASA Astrophysics Data System (ADS)

    Jana, Atanu; Das, Kinsuk; Konar, Saugata; Dhara, Anamika; Biswas, Sujan; Chatterjee, Sudipta; Mondal, Tapan Kumar

    2015-11-01

    Two novel complexes [Mn2(phmp)2](ClO4)2 (1) and [Ni2(phmp)(μ-H2O)(H2O)4](NO3)3 (2) were synthesized using an "end-off" compartmental ligand [H-phmp = 4-Methyl-2,6-bis-(pyridin-2-yl-hydrazonomethyl)-phenol] with Mn(II)-perchlorate and Ni(II)-nitrate salts as metal precursors. Both these complexes were characterized by spectroscopic (IR, UV-Vis) and X-ray crystal structure analysis. The ligand, H-phmp acts as a pentadentate NNONN donor for both the metal complexes and the geometry of the complexes 1 and 2 is distorted octahedral. The DFT optimized bond distances and angles are well correlate to the X-ray structure bond parameters. For complex 1 the transitions at 435 nm and 428 nm have mixed MLCT (dπ(Mn) → π*(L)) and ILCT (π(L) → π*(L)) character whereas other transitions correspond to intra-ligand charge transfer transitions (ILCT). For complex 2, weak transitions at 464 and 405 nm correspond to ligand to metal charge transfer transitions (LMCT) (π(L) → dπ(Ni)) and most of the other transitions have ILCT character. As anticipated, various weak forces, i.e. anion-π/π-anion/anion-π/π-NH interactions as well as C-H/π interaction, play a key role in stabilizing the self-assembly process observed for both compounds.

  19. Construction of synthetic nucleoli and what it tells us about propagation of sub-nuclear domains through cell division

    PubMed Central

    Grob, Alice; McStay, Brian

    2014-01-01

    The cell nucleus is functionally compartmentalized into numerous membraneless and dynamic, yet defined, bodies. The cell cycle inheritance of these nuclear bodies (NBs) is poorly understood at the molecular level. In higher eukaryotes, their propagation is challenged by cell division through an “open” mitosis, where the nuclear envelope disassembles along with most NBs. A deeper understanding of the mechanisms involved can be achieved using the engineering principles of synthetic biology to construct artificial NBs. Successful biogenesis of such synthetic NBs demonstrates knowledge of the basic mechanisms involved. Application of this approach to the nucleolus, a paradigm of nuclear organization, has highlighted a key role for mitotic bookmarking in the cell cycle propagation of NBs. PMID:25486191

  20. SINE (selective inhibitor of nuclear export)--translational science in a new class of anti-cancer agents.

    PubMed

    Gerecitano, John

    2014-01-01

    Regulation of protein trafficking between the nucleus and cytoplasm represents a novel control point for antineoplastic intervention. Several proteins involved with cellular growth and survival depend on precise and timely positioning within the cell to fulfill their functions, and the nuclear membrane defines one of the most important compartmental barriers. Chromosome Region Maintenance 1, or exportin-1 (CRM1/XPO1), is involved with the export of more than 200 nuclear proteins, and has intriguingly been shown to have an increased expression in several tumor cell types. Selinexor (KPT-330) is a first-in-class selective inhibitor of nuclear export (SINE) to be developed for clinical use. Preclinical data has demonstrated antineoplastic activity of SINE compounds in many human solid and hematologic malignancies. The clinical development of Selinexor provides an excellent model for translational research. PMID:25281264

  1. Nuclear astrophysics

    SciTech Connect

    Haxton, W.C.

    1992-12-31

    The problem of core-collapse supernovae is used to illustrate the many connections between nuclear astrophysics and the problems nuclear physicists study in terrestrial laboratories. Efforts to better understand the collapse and mantle ejection are also motivated by a variety of interdisciplinary issues in nuclear, particle, and astrophysics, including galactic chemical evolution, neutrino masses and mixing, and stellar cooling by the emission of new particles. The current status of theory and observations is summarized.

  2. Nuclear astrophysics

    SciTech Connect

    Haxton, W.C.

    1992-01-01

    The problem of core-collapse supernovae is used to illustrate the many connections between nuclear astrophysics and the problems nuclear physicists study in terrestrial laboratories. Efforts to better understand the collapse and mantle ejection are also motivated by a variety of interdisciplinary issues in nuclear, particle, and astrophysics, including galactic chemical evolution, neutrino masses and mixing, and stellar cooling by the emission of new particles. The current status of theory and observations is summarized.

  3. Nuclear APC.

    PubMed

    Neufeld, Kristi L

    2009-01-01

    Mutational inactivation of the tumor suppressor gene APC (Adenomatous polyposis coli) is thought to be an initiating step in the progression of the vast majority ofcolorectal cancers. Attempts to understand APC function have revealed more than a dozen binding partners as well as several subcellular localizations including at cell-cell junctions, associated with microtubules at the leading edge of migrating cells, at the apical membrane, in the cytoplasm and in the nucleus. The present chapter focuses on APC localization and functions in the nucleus. APC contains two classical nuclear localization signals, with a third domain that can enhance nuclear import. Along with two sets of nuclear export signals, the nuclear localization signals enable the large APC protein to shuttle between the nucleus and cytoplasm. Nuclear APC can oppose beta-catenin-mediated transcription. This down-regulation of nuclear beta-catenin activity by APC most likely involves nuclear sequestration of beta-catenin from the transcription complex as well as interaction of APC with transcription corepressor CtBP. Additional nuclear binding partners for APC include transcription factor activator protein AP-2alpha, nuclear export factor Crm1, protein tyrosine phosphatase PTP-BL and perhaps DNA itself. Interaction of APC with polymerase beta and PCNA, suggests a role for APC in DNA repair. The observation that increases in the cytoplasmic distribution of APC correlate with colon cancer progression suggests that disruption of these nuclear functions of APC plays an important role in cancer progression. APC prevalence in the cytoplasm of quiescent cells points to a potential function for nuclear APC in control of cell proliferation. Clear definition of APC's nuclear function(s) will expand the possibilities for early colorectal cancer diagnostics and therapeutics targeted to APC. PMID:19928349

  4. Neuropathogenic SIVsmmFGb Genetic Diversity and Selection-Induced Tissue-Specific Compartmentalization During Chronic Infection and Temporal Evolution of Viral Genes in Lymphoid Tissues and Regions of the Central Nervous System

    PubMed Central

    Reeve, Aaron B.; Pearce, Nicholas C.; Patel, Kalpana; Augustus, Katherine V.

    2010-01-01

    Abstract SIVsmmFGb is a lentivirus swarm that induces neuropathology in over 90% of infected pigtailed macaques and reliably models central nervous system HIV infection in people. We have previously studied SIVsmmFGb genetic diversity and compartmentalization during acute infection, but little is understood about diversity and intertissue compartmentalization during chronic infection. Tissue-specific pressure appeared to affect the diversity of Nef sequences between tissues, but changes to the Env V1 region and Int diversity were similar across all tissues. At 2 months postinfection, compartmentalization of the SIVsmmFGb env V1 region, nef, and int was noted between different brain regions and between brain regions and lymph nodes. Convergent evolution of the nef and env V1 region, and divergent evolution of int, was noted between compartments and all genes demonstrated intratissue temporal segregation. For the env V1 region and nef, temporal segregation was stronger in the brain regions than the periphery, but little difference between tissues was noted for int. Positive selection of the env V1 region appeared in most tissues at 2 months postinfection, whereas nef and int faced negative selection in all tissues. Positive selection of the env V1 region sequences increased in some brain regions over time. SIVsmmFGb nef and int sequences each saw increased negative selection in brain regions, and one lymph node, over the course of infection. Functional differences between tissue compartments decreased over time for int and env V1 region sequences, but increased for nef sequences. PMID:20518690

  5. Ultra–Short-Term Reproducibility of Speckle-Noise Freed Fluid and Tissue Compartmentalization of the Choroid Analyzed by Standard OCT

    PubMed Central

    Maloca, Peter; Gyger, Cyrill; Schoetzau, Andreas; Hasler, Pascal W.

    2015-01-01

    Purpose We measured reproducibility of speckle-noise freed fluid and tissue compartmentalization of the choroid (choroidal angiography and tissue characterization). Methods This study included 26 eyes of 13 healthy females: 13 were used for repeated measurements and 13 were used for side comparison. A semiautomated algorithm removed speckle-noise with structure preservation. Results Intraclass correlation (ICC), with respect to reproducibility of the method, showed an ICC for choroidal fluid inner space analysis (FISA) of 95.15% (90.01–98.24). The ICC of tissue inner space analysis (TISA) was 99.75% (99.47–99.91). The total choroid ratio (TCR), calculated from volumes of tissue to vessels, showed an ICC of 88.84% (78.28–95.82). Comparison of eyes (left to right) showed a difference for FISA of 0.033 (95% confidence interval [CI] −0.0018–0.0680, P = 0.063), TISA −0.118 (CI −0.2373–0.0023, P = 0.055), and TCR −0.590 (CI −0.9047 to −0.2754, P = 0.004). The ICC for FISA and TISA showed a trend in the difference comparing left and right eyes; however, TCR showed a significant difference between the eyes in the measured area (P < 0.001). Mean overall FISA was 0.58 mm3 (range, 0.25–0.98 mm3, SD = 0.14). Mean TISA was 3.45 mm3 (range, 2.38–5.0 mm3, SD 0.072). Mean TCR was 6.13 (overall range, 3.93–10.2, SD = 1.34). Conclusions Differences in choroidal layers between subjects were found mainly due to alterations in choroidal tissue. Reproducibility of speckle-noise freed choroidal angiography appeared excellent. Translational Relevance Speckle noise is a granular “noise” that appears in a wide range of medical imaging methods as ultrasonography, magnetic resonance, computer tomography, or optical coherence tomography (OCT). Findings from basic science about speckle noise were translated into a novel, medical image postprocessing application that can separate signal from speckle noise with structure preservation with high reproducibility and

  6. Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations

    PubMed Central

    Van Laethem, Kristel; Gomes, Perpetua; Baele, Guy; Pineda-Peña, Andrea-Clemencia; Vandamme, Anne-Mieke; Camacho, Ricardo J.; Abecasis, Ana B.

    2016-01-01

    Abstract Objective: The latest nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) is indicated for human immunodeficiency virus type-1 (HIV-1) patients initiating antiretroviral treatment, but the extent of genotypic RPV resistance in treatment-naive patients outside clinical trials is poorly defined. Study Design: This retrospective observational study of clinical data from Belgium and Portugal evaluates genotypic information from HIV-1 drug-naive patients obtained for the purpose of drug resistance testing. Rilpivirine resistance-associated mutations (RPV-RAMs) were defined based on clinical trials, phenotypic studies, and expert-based resistance algorithms. Viral susceptibility to RPV alone and to the single-tablet regimen was estimated using expert-based resistance algorithms. Results: In 4,631 HIV-1 treatment-naive patients infected with diverse HIV-1 subtypes, major RPV-RAMs were detected in 4.6%, while complete viral susceptibility to RPV was estimated in 95% of patients. Subtype C- and F1-infected patients displayed the highest levels of reduced viral susceptibility at baseline, respectively 13.2% and 9.3%, mainly due to subtype- and geographic-dependent occurrence of RPV-RAMs E138A and A98G as natural polymorphisms. Strikingly, a founder effect in Portugal resulted in a 138A prevalence of 13.2% in local subtype C-infected treatment-naive patients. The presence of transmitted drug resistance did not impact our estimates. Conclusion: RPV is the first HIV-1 inhibitor for which, in the absence of transmitted drug resistance, intermediate or high-level genotypic resistance can be detected in treatment-naive patients. The extent of RPV susceptibility in treatment-naive patients differs depending on the HIV-1 subtype and dynamics of local compartmentalized epidemics. The highest prevalence of reduced susceptibility was found to be 15.7% in Portuguese subtype C-infected treatment-naive patients. In this context, even in the absence of

  7. Development and compartmentalization of chalky carbonate reservoirs: The Urgonian Jura-Bas Dauphiné platform model (Génissiat, southeastern France)

    NASA Astrophysics Data System (ADS)

    Richard, J.; Sizun, J. P.; Machhour, L.

    2007-06-01

    The chalky limestones of the upper Barremian-middle Aptian Urgonian Limestone Formation of the Jura-Bas Dauphiné platform (southeastern France) are characterised by a total porosity between 17.9 and 24.5%, a threshold radius between 1.04 and 2.13 μm, a trapped porosity between 51.4 and 68.3% and a gas permeability between 161 and 410 mD. They were formed in response to the diagenetic evolution of dominantly micritic sediments deposited during a "calcite sea" interval. Their present-day reservoir qualities and transport properties are controlled by the intercrystalline microporosity of microcrystalline areas (peloids or matrix). This intercrystalline microporosity is the product of a meteoric porewater input (installation of a shallow-burial phreatic environment characterised by a short residence time of porewaters) which promoted an aggrading neomorphism (Ostwald ripening process). The impact of the burial diagenesis on the reservoir qualities and the transport properties of these chalky limestones is limited. The chalky units are presently compartmentalized by horizontal layers of compact limestones characterised by a total porosity between 2.9 and 4.5%, a threshold radius between 0.04 and 0.09 μm, a trapped porosity of 92.4-92.8% and a gas permeability of 2 mD. Like the chalky limestones, the present-day reservoir qualities and transport properties of compact limestones are controlled by the intercrystalline microporosity of microcrystalline areas. The petrophysical differences between the chalky and compact limestones result from differences in the pore network of microcrystalline areas due to an increase in the average size of particles and a modification of crystal-crystal contacts. These petrographical differences reflect an evolution of micritic areas of original sediments during submarine lithifications (precipitation of microcrystalline cements within the pore space and/or an increase in solid-solid contacts by crystal growth) which preceded the

  8. Cellular compartmentalization of secondary metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors sh...

  9. Nuclear safety

    NASA Technical Reports Server (NTRS)

    Buden, D.

    1991-01-01

    Topics dealing with nuclear safety are addressed which include the following: general safety requirements; safety design requirements; terrestrial safety; SP-100 Flight System key safety requirements; potential mission accidents and hazards; key safety features; ground operations; launch operations; flight operations; disposal; safety concerns; licensing; the nuclear engine for rocket vehicle application (NERVA) design philosophy; the NERVA flight safety program; and the NERVA safety plan.

  10. Nuclear stress test

    MedlinePlus

    ... Persantine stress test; Thallium stress test; Stress test - nuclear; Adenosine stress test; Regadenoson stress test; CAD - nuclear stress; Coronary artery disease - nuclear stress; Angina - nuclear ...

  11. Parvovirus Induced Alterations in Nuclear Architecture and Dynamics

    PubMed Central

    Ihalainen, Teemu O.; Niskanen, Einari A.; Jylhävä, Juulia; Paloheimo, Outi; Dross, Nicolas; Smolander, Hanna; Langowski, Jörg; Timonen, Jussi; Vihinen-Ranta, Maija

    2009-01-01

    The nucleus of interphase eukaryotic cell is a highly compartmentalized structure containing the three-dimensional network of chromatin and numerous proteinaceous subcompartments. DNA viruses induce profound changes in the intranuclear structures of their host cells. We are applying a combination of confocal imaging including photobleaching microscopy and computational methods to analyze the modifications of nuclear architecture and dynamics in parvovirus infected cells. Upon canine parvovirus infection, expansion of the viral replication compartment is accompanied by chromatin marginalization to the vicinity of the nuclear membrane. Dextran microinjection and fluorescence recovery after photobleaching (FRAP) studies revealed the homogeneity of this compartment. Markedly, in spite of increase in viral DNA content of the nucleus, a significant increase in the protein mobility was observed in infected compared to non-infected cells. Moreover, analyzis of the dynamics of photoactivable capsid protein demonstrated rapid intranuclear dynamics of viral capsids. Finally, quantitative FRAP and cellular modelling were used to determine the duration of viral genome replication. Altogether, our findings indicate that parvoviruses modify the nuclear structure and dynamics extensively. Intranuclear crowding of viral components leads to enlargement of the interchromosomal domain and to chromatin marginalization via depletion attraction. In conclusion, parvoviruses provide a useful model system for understanding the mechanisms of virus-induced intranuclear modifications. PMID:19536327

  12. Nuclear PI3K signaling in cell growth and tumorigenesis

    PubMed Central

    Davis, William J.; Lehmann, Peter Z.; Li, Weimin

    2015-01-01

    The PI3K/Akt signaling pathway is a major driving force in a variety of cellular functions. Dysregulation of this pathway has been implicated in many human diseases including cancer. While the activity of the cytoplasmic PI3K/Akt pathway has been extensively studied, the functions of these molecules and their effector proteins within the nucleus are poorly understood. Harboring key cellular processes such as DNA replication and repair as well as nascent messenger RNA transcription, the nucleus provides a unique compartmental environment for protein–protein and protein–DNA/RNA interactions required for cell survival, growth, and proliferation. Here we summarize recent advances made toward elucidating the nuclear PI3K/Akt signaling cascade and its key components within the nucleus as they pertain to cell growth and tumorigenesis. This review covers the spatial and temporal localization of the major nuclear kinases having PI3K activities and the counteracting phosphatases as well as the role of nuclear PI3K/Akt signaling in mRNA processing and exportation, DNA replication and repair, ribosome biogenesis, cell survival, and tumorigenesis. PMID:25918701

  13. Androgen receptor regulates nuclear trafficking and nuclear domain residency of corepressor HDAC7 in a ligand-dependent fashion

    SciTech Connect

    Karvonen, Ulla; Jaenne, Olli A.; Palvimo, Jorma J. . E-mail: jorma.palvimo@uku.fi

    2006-10-01

    In addition to chromosomal proteins, histone deacetylases (HDACs) target transcription factors in transcriptional repression. Here, we show that the class II HDAC family member HDAC7 is an efficient corepressor of the androgen receptor (AR). HDAC7 resided in the cytoplasm in the absence of AR or a cognate ligand, but hormone-occupancy of AR induced nuclear transfer of HDAC7. Nuclear colocalization pattern of AR and HDAC7 was dependent on the nature of the ligand. In the presence of testosterone, a portion of HDAC7 localized to pearl-like nuclear domains, whereas AR occupied with antagonistic ligands cyproterone acetate- or casodex (bicalutamide) recruited HDAC7 from these domains to colocalize with the receptor in speckles and nucleoplasm in a more complete fashion. Ectopic expression of PML-3 relieved the repressive effect of HDAC7 on AR function by sequestering HDAC7 to PML-3 domains. AR acetylation at Lys630/632/633 was not the target of HDAC7 repression, since repression of AR function was independent of these acetylation sites. Moreover, the deacetylase activity of HDAC7 was in part dispensable in the repression of AR function. In sum, our results identify HDAC7 as a novel AR corepressor whose subcellular and subnuclear compartmentalization can be regulated in an androgen-selective manner.

  14. Nuclear Speckles

    PubMed Central

    Spector, David L.; Lamond, Angus I.

    2011-01-01

    Nuclear speckles, also known as interchromatin granule clusters, are nuclear domains enriched in pre-mRNA splicing factors, located in the interchromatin regions of the nucleoplasm of mammalian cells. When observed by immunofluorescence microscopy, they usually appear as 20–50 irregularly shaped structures that vary in size. Speckles are dynamic structures, and their constituents can exchange continuously with the nucleoplasm and other nuclear locations, including active transcription sites. Studies on the composition, structure, and dynamics of speckles have provided an important paradigm for understanding the functional organization of the nucleus and the dynamics of the gene expression machinery. PMID:20926517

  15. (Nuclear theory). [Research in nuclear physics

    SciTech Connect

    Haxton, W.

    1990-01-01

    This report discusses research in nuclear physics. Topics covered in this paper are: symmetry principles; nuclear astrophysics; nuclear structure; quark-gluon plasma; quantum chromodynamics; symmetry breaking; nuclear deformation; and cold fusion. (LSP)

  16. Nuclear forces

    SciTech Connect

    Machleidt, R.

    2013-06-10

    These lectures present an introduction into the theory of nuclear forces. We focus mainly on the modern approach, in which the forces between nucleons emerge from low-energy QCD via chiral effective field theory.

  17. NUCLEAR REACTOR

    DOEpatents

    Sherman, J.; Sharbaugh, J.E.; Fauth, W.L. Jr.; Palladino, N.J.; DeHuff, P.G.

    1962-10-23

    A nuclear reactor incorporating seed and blanket assemblies is designed. Means are provided for obtaining samples of the coolant from the blanket assemblies and for varying the flow of coolant through the blanket assemblies. (AEC)

  18. Nuclear battlefields

    SciTech Connect

    Arkin, W.M.; Fieldhouse, R.W.

    1985-01-01

    This book provides complete data on the nuclear operations and research facilities in the U.S.A., the U.S.S.R., France, China and the U.K. It describes detailed estimates on the U.S.S.R.'s nuclear stockpile for over 500 locations. It shows how non-nuclear countries cooperate with the world-wide war machine. And it maps the U.S. nuclear facilities from Little America, WY, and Charleston, SC, to the battleships patroling the world's oceans and subs stalking under the sea. The data were gathered from unclassified sources through the Freedom of Information Act, from data supplied to military installations, and from weapons source books. It provides guidance for policymakers, government and corporate officials.

  19. Nuclear Data

    SciTech Connect

    White, Morgan C.

    2014-01-23

    PowerPoint presentation targeted for educational use. Nuclear data comes from a variety of sources and in many flavors. Understanding where the data you use comes from and what flavor it is can be essential to understand and interpret your results. This talk will discuss the nuclear data pipeline with particular emphasis on providing links to additional resources that can be used to explore the issues you will encounter.

  20. Nuclear Nonproliferation

    SciTech Connect

    Atkins-Duffin, C E

    2008-12-10

    With an explosion equivalent of about 20kT of TNT, the Trinity test was the first demonstration of a nuclear weapon. Conducted on July 16, 1945 in Alamogordo, NM this site is now a Registered National Historic Landmark. The concept and applicability of nuclear power was demonstrated on December 20, 1951 with the Experimental Breeder Reactor Number One (EBR-1) lit four light bulbs. This reactor is now a Registered National Historic Landmark, located near Arco, ID. From that moment forward it had been clearly demonstrated that nuclear energy has both peaceful and military applications and that the civilian and military fuel cycles can overlap. For the more than fifty years since the Atoms for Peace program, a key objective of nuclear policy has been to enable the wider peaceful use of nuclear energy while preventing the spread of nuclear weapons. Volumes have been written on the impact of these two actions on the world by advocates and critics; pundits and practioners; politicians and technologists. The nations of the world have woven together a delicate balance of treaties, agreements, frameworks and handshakes that are representative of the timeframe in which they were constructed and how they have evolved in time. Collectively these vehicles attempt to keep political will, nuclear materials and technology in check. This paper captures only the briefest abstract of the more significant aspects on the Nonproliferation Regime. Of particular relevance to this discussion is the special nonproliferation sensitivity associated with the uranium isotope separation and spent fuel reprocessing aspects of the nuclear fuel cycle.

  1. Fluid flow compartmentalization in the Sicilian fold and thrust belt: Implications for the regional aqueous fluid flow and oil migration history

    NASA Astrophysics Data System (ADS)

    Dewever, B.; Swennen, R.; Breesch, L.

    2013-04-01

    calcite has less depleted δ18O values compared to calcite of types 1 and 2 and the δ18O from calcite in faults is even positive. During the final stages of fluid flow with precipitation of calcite type 3, the fluid flow model invokes infiltration of overpressured fluids that migrated along the décollement zone. These fluids only infiltrate the thrust sheet in the hanging wall of the thrust, leading to a compartmentalized fluid flow pattern. An identical fluid flow pattern with migration of low and hot saline fluids, associated with hydrocarbons, was observed in other parts of the Sicilian fold and thrust belt. With identical structural deformation and fluid flow patterns, the study confirms the suitability of the frontal part of the Sicilian fold and thrust belt as an outcrop analog for deeply submerged accretionary prisms. The study thus offers unique insights in expected fluid flow patterns in thrust sheets of deeply submerged accretionary complexes.

  2. Nuclear risk

    SciTech Connect

    Levenson, M.

    1989-01-01

    The title of our session, Nuclear Risk Versus Other Power Options, is provocative. It is also a title with different meanings to different people. To the utility chief executive officer, nuclear power is a high-risk financial undertaking because of political and economic barriers to cost recovery. To the utility dispatcher, it is a high-risk future power source since plant completion and start-up dates can be delayed for very long times due to uncertain legal and political issues. To the environmentalist, concerned about global effects such as greenhouse and acid rain, nuclear power is a relatively low risk energy source. To the financial people, nuclear power is a cash cow turned sour because of uncertainties as to what new plants will cost and whether they will even be allowed to operate. The statistics on risk are known and the results of probability risk assessment calculations of risks are known. The challenge is not to make nuclear power safer, it is already one of the safest, if not the safest, source of power currently available. The challenge is to find a way to communicate this to the public.

  3. Restoration of nuclear-import failure caused by triple A syndrome and oxidative stress

    SciTech Connect

    Kiriyama, Takao; Hirano, Makito Asai, Hirohide; Ikeda, Masanori; Furiya, Yoshiko; Ueno, Satoshi

    2008-10-03

    Triple A syndrome is an autosomal recessive neurological disease, mimicking motor neuron disease, and is caused by mutant ALADIN, a nuclear-pore complex component. We recently discovered that the pathogenesis involved impaired nuclear import of DNA repair proteins, including DNA ligase I and the cerebellar ataxia causative protein aprataxin. Such impairment was overcome by fusing classical nuclear localization signal (NLS) and 137-aa downstream sequence of XRCC1, designated stretched NLS (stNLS). We report here that the minimum essential sequence of stNLS (mstNLS) is residues 239-276, downsized by more than 100 aa. mstNLS enabled efficient nuclear import of DNA repair proteins in patient fibroblasts, functioned under oxidative stress, and reduced oxidative-stress-induced cell death, more effectively than stNLS. The stress-tolerability of mstNLS was also exerted in control fibroblasts and neuroblastoma cells. These findings may help develop treatments for currently intractable triple A syndrome and other oxidative-stress-related neurological diseases, and contribute to nuclear compartmentalization study.

  4. Krüppel-like factor 9 regulates cell proliferation and compartmental expression of estrogen and progesterone receptors in the mouse uterine endometrium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The uterine endometrium undergoes dynamic changes in proliferation and differentiation in response to estrogen (E) and progesterone (P) during the estrous cycle and pregnancy. E and P exert their functions through their respective nuclear receptors, estrogen receptor (ESR) and progesterone receptor ...

  5. Nuclear astrophysics

    NASA Astrophysics Data System (ADS)

    Penionzhkevich, Yu. E.

    2010-08-01

    The International Year of Astronomy 2009 (IYA2009) was declared by the 62nd General Assembly of the United Nations and was also endorsed by UNESCO. Investigations in the realms of particle and nuclear physicsmake a large contribution in the development of our ideas of the properties of the Universe. The present article discusses some problems of the evolution of the Universe, nucleosyntheses, and cosmochronology from the point of view of nuclear and particle physics. Processes occurring in the Universe are compared with the mechanisms of the production and decay of nuclei, as well as with the mechanisms of their interaction at high energies. Examples that demonstrate the potential of nuclearphysics methods for studying cosmic objects and the properties of the Universe are given. The results that come from investigations into nuclear reactions induced by beams of radioactive nuclei and which make it possible to take a fresh look at the nucleosynthesis scenario in the range at light nuclei are presented.

  6. Nuclear scales

    SciTech Connect

    Friar, J.L.

    1998-12-01

    Nuclear scales are discussed from the nuclear physics viewpoint. The conventional nuclear potential is characterized as a black box that interpolates nucleon-nucleon (NN) data, while being constrained by the best possible theoretical input. The latter consists of the longer-range parts of the NN force (e.g., OPEP, TPEP, the {pi}-{gamma} force), which can be calculated using chiral perturbation theory and gauged using modern phase-shift analyses. The shorter-range parts of the force are effectively parameterized by moments of the interaction that are independent of the details of the force model, in analogy to chiral perturbation theory. Results of GFMC calculations in light nuclei are interpreted in terms of fundamental scales, which are in good agreement with expectations from chiral effective field theories. Problems with spin-orbit-type observables are noted.

  7. Nuclear pursuits

    SciTech Connect

    Not Available

    1993-05-01

    This table lists quantities of warheads (in stockpile, peak number per year, total number built, number of known test explosions), weapon development milestones (developers of the atomic bomb and hydrogen bomb, date of first operational ICBM, first nuclear-powered naval SSN in service, first MIRVed missile deployed), and testing milestones (first fission test, type of boosted fission weapon, multistage thermonuclear test, number of months from fission bomb to multistage thermonuclear bomb, etc.), and nuclear infrastructure (assembly plants, plutonium production reactors, uranium enrichment plants, etc.). Countries included in the tally are the United States, Soviet Union, Britain, France, and China.

  8. Nuclear power: Fourth edition

    SciTech Connect

    Deutsch, R.W.

    1986-01-01

    This book describes the basics of nuclear power generation, explaining both the benefits and the real and imagined risks of nuclear power. It includes a discussion of the Three Mile Island accident and its effects. Nuclear Power has been used in the public information programs of more than 100 utilities. The contents discussed are: Nuclear Power and People; Why Nuclear Power. Electricity produced by coal; Electricity produced by nuclear fuel; Nuclear plant sites in the United States; Short History of Commercial Nuclear Power; U.S. nuclear submarines, Regulation of Nuclear Power Plants; Licensing process, Nuclear Power Plant Operator Training; Nuclear power plant simulator, Are Nuclear Plants Safe.; Containment structure, Nuclear Power Plant Insurance; Is Radiation Dangerous.; Man-made radiation, What is Nuclear Fuel.; Fuel cycle for commercial nuclear power plants; Warm Water Discharge; Cooling tower; Protection of Radioactive Materials; Plutonium and Proliferation; Disposal of Radioactive Wastes; Are Alternate Energy Sources Available.; Nuclear Opposition; and Nuclear Power in the Future.

  9. The DEAD-box helicase DDX3 substitutes for the cap-binding protein eIF4E to promote compartmentalized translation initiation of the HIV-1 genomic RNA.

    PubMed

    Soto-Rifo, Ricardo; Rubilar, Paulina S; Ohlmann, Théophile

    2013-07-01

    Here, we show a novel molecular mechanism promoted by the DEAD-box RNA helicase DDX3 for translation of the HIV-1 genomic RNA. This occurs through the adenosine triphosphate-dependent formation of a translation initiation complex that is assembled at the 5' m(7)GTP cap of the HIV-1 mRNA. This is due to the property of DDX3 to substitute for the initiation factor eIF4E in the binding of the HIV-1 m(7)GTP 5' cap structure where it nucleates the formation of a core DDX3/PABP/eIF4G trimeric complex on the HIV-1 genomic RNA. By using RNA fluorescence in situ hybridization coupled to indirect immunofluorescence, we further show that this viral ribonucleoprotein complex is addressed to compartmentalized cytoplasmic foci where the translation initiation complex is assembled. PMID:23630313

  10. Nuclear Terrorism.

    SciTech Connect

    Hecker, Siegfried S.

    2001-01-01

    As pointed out by several speakers, the level of violence and destruction in terrorist attacks has increased significantly during the past decade. Fortunately, few have involved weapons of mass destruction, and none have achieved mass casualties. The Aum Shinrikyo release of lethal nerve agent, sarin, in the Tokyo subway on March 20, 1995 clearly broke new ground by crossing the threshold in attempting mass casualties with chemical weapons. However, of all weapons of mass destruction, nuclear weapons still represent the most frightening threat to humankind. Nuclear weapons possess an enormous destructive force. The immediacy and scale of destruction are unmatched. In addition to destruction, terrorism also aims to create fear among the public and governments. Here also, nuclear weapons are unmatched. The public's fear of nuclear weapons or, for that matter, of all radioactivity is intense. To some extent, this fear arises from a sense of unlimited vulnerability. That is, radioactivity is seen as unbounded in three dimensions - distance, it is viewed as having unlimited reach; quantity, it is viewed as having deadly consequences in the smallest doses (the public is often told - incorrectly, of course - that one atom of plutonium will kill); and time, if it does not kill you immediately, then it will cause cancer decades hence.

  11. Nuclear medicine

    SciTech Connect

    Wagner, H.N. Jr.

    1986-10-17

    In 1985 and 1986 nuclear medicine became more and more oriented toward in vov chemistry, chiefly as a result of advances in positron emission tomography (PET). The most important trend was the extension of PET technology into the care of patients with brain tumors, epilepsy, and heart disease. A second trend was the increasing use of single-photon emission computed tomography (SPECT).

  12. Nuclear energy.

    PubMed

    Wilson, Peter D

    2010-01-01

    The technical principles and practices of the civil nuclear industry are described with particular reference to fission and its products, natural and artificial radioactivity elements principally concerned and their relationships, main types of reactor, safety issues, the fuel cycle, waste management, issues related to weapon proliferation, environmental considerations and possible future developments. PMID:21180342

  13. Nuclear Science.

    ERIC Educational Resources Information Center

    Pennsylvania State Dept. of Education, Harrisburg. Bureau of Curriculum Services.

    This document is a report on a course in nuclear science for the high school curriculum. The course is designed to provide a basic but comprehensive understanding of the atom in the light of modern knowledge, and to show how people attempt to harness the tremendous energy liberated through fission and fusion reactions. The course crosses what are…

  14. Nuclear Misinformation

    ERIC Educational Resources Information Center

    Ford, Daniel F.; Kendall, Henry W.

    1975-01-01

    Many scientists feel that research into nuclear safety has been diverted or distorted, and the results of the research concealed or inaccurately reported on a large number of occasions. Of particular concern have been the emergency cooling systems which have not, as yet, been adequately tested. (Author/MA)

  15. A novel nuclear localization signal in the auxiliary domain of apobec-1 complementation factor regulates nucleocytoplasmic import and shuttling.

    PubMed

    Blanc, Valerie; Kennedy, Susan; Davidson, Nicholas O

    2003-10-17

    C to U editing of the nuclear apolipoprotein B (apoB) transcript is mediated by a core enzyme containing a catalytic deaminase, apobec-1, and an RNA binding subunit, apobec-1 complementation factor (ACF). ACF expression is predominantly nuclear, including mutant proteins with deletions of a putative nuclear localization signal. We have now identified a novel 41-residue motif (ANS) in the auxiliary domain of ACF that functions as an authentic nuclear localization signal. ANS-green fluorescence protein and ANS-beta-galactosidase chimeras were both expressed exclusively in the nucleus, whereas wild-type chimeras or an ACF deletion mutant lacking the ANS were cytoplasmic. Nuclear accumulation of ACF is transcription-dependent, temperature-sensitive, and reversible, features reminiscent of a shuttling protein. ACF relocates to the cytoplasm after actinomycin D treatment, an effect blocked by the CRM1 inhibitor leptomycin B. Heterokaryon assays confirmed directly that ACF shuttles in vivo. ACF binds to the protein carrier, transportin 2 in vivo, and colocalizes to the nucleus as determined by confocal microscopy. Co-immunoprecipitation experiments revealed that transportin 2 binds directly to the ANS motif. These data suggest that directed nuclear localization and compartmentalization of the core complex of the apoB RNA editing enzyme is regulated through a dominant targeting sequence (ANS) contained within ACF. PMID:12896982

  16. Cytoplasmic and nuclear cytokine receptor complexes.

    PubMed

    Mertani, H C; Morel, G; Lobie, P E

    1999-01-01

    Much of our understanding on how hormones and cytokines transmit their message into the cell is based on the receptor activation at the plasma membrane. Many experimental in vitro models have established the paradigm for cytokine action based upon such activation of their cell surface receptor. The signaling from the plasma membrane activated cytokine receptor is driven to the nucleus by a rapid ricochet of protein phosphorylation, ultimately integrated as a differentiative, proliferative, or transcriptional message. The Janus kinase (JAK)--signal transducers and activators of transcription (STAT) pathway that was first thought to be cytokine receptor specific now appears to be activated by other noncytokine receptors. Also, evidence is accumulating showing that cytokines modulate the signal transduction machinery of the tyrosine kinase receptors and that of the heterotrimeric guanosine triphosphate (GTP)-binding protein-coupled receptors. Thus cytokine receptor signaling has become much more complex than originally hypothesized, challenging the established model of specificity of the action of a given cytokine. This review is focused on another level of complexity emerging within cytokine receptor superfamily signaling. Over the past 10 years, data from different laboratories have shown that cytokines and their receptors localize to intracellular compartments including the nucleus, and, in some cases, biological responses have been correlated with this unexpected location, raising the possibility that cytokines act as their own messenger through inter-actions with nuclear proteins. Thus, the interplay between cytokine receptor engagement and cellular signaling turns out to be more dynamic than originally suspected. The mechanisms and regulations of intracellular translocation of the cytokines, their receptors, and their signaling proteins are discussed in the context that such compartmentalization provides some of the specificity of the responses mediated by each

  17. NUCLEAR REACTOR

    DOEpatents

    Anderson, C.R.

    1962-07-24

    A fluidized bed nuclear reactor and a method of operating such a reactor are described. In the design means are provided for flowing a liquid moderator upwardly through the center of a bed of pellets of a nentron-fissionable material at such a rate as to obtain particulate fluidization while constraining the lower pontion of the bed into a conical shape. A smooth circulation of particles rising in the center and falling at the outside of the bed is thereby established. (AEC)

  18. NUCLEAR REACTORS

    DOEpatents

    Long, E.; Ashby, J.W.

    1958-09-16

    ABS>A graphite moderator structure is presented for a nuclear reactor compriscd of an assembly of similarly orientated prismatic graphite blocks arranged on spaced longitudinal axes lying in common planes wherein the planes of the walls of the blocks are positioned so as to be twisted reintive to the planes of said axes so thatthe unlmpeded dtrect paths in direction wholly across the walls of the blocks are limited to the width of the blocks plus spacing between the blocks.

  19. NUCLEAR REACTOR

    DOEpatents

    Grebe, J.J.

    1959-07-14

    High temperature reactors which are uniquely adapted to serve as the heat source for nuclear pcwered rockets are described. The reactor is comprised essentially of an outer tubular heat resistant casing which provides the main coolant passageway to and away from the reactor core within the casing and in which the working fluid is preferably hydrogen or helium gas which is permitted to vaporize from a liquid storage tank. The reactor core has a generally spherical shape formed entirely of an active material comprised of fissile material and a moderator material which serves as a diluent. The active material is fabricated as a gas permeable porous material and is interlaced in a random manner with very small inter-connecting bores or capillary tubes through which the coolant gas may flow. The entire reactor is divided into successive sections along the direction of the temperature gradient or coolant flow, each section utilizing materials of construction which are most advantageous from a nuclear standpoint and which at the same time can withstand the operating temperature of that particular zone. This design results in a nuclear reactor characterized simultaneously by a minimum critiral size and mass and by the ability to heat a working fluid to an extremely high temperature.

  20. Nuclear waste

    SciTech Connect

    Not Available

    1991-09-01

    Radioactive waste is mounting at U.S. nuclear power plants at a rate of more than 2,000 metric tons a year. Pursuant to statute and anticipating that a geologic repository would be available in 1998, the Department of Energy (DOE) entered into disposal contracts with nuclear utilities. Now, however, DOE does not expect the repository to be ready before 2010. For this reason, DOE does not want to develop a facility for monitored retrievable storage (MRS) by 1998. This book is concerned about how best to store the waste until a repository is available, congressional requesters asked GAO to review the alternatives of continued storage at utilities' reactor sites or transferring waste to an MRS facility, GAO assessed the likelihood of an MRSA facility operating by 1998, legal implications if DOE is not able to take delivery of wastes in 1998, propriety of using the Nuclear Waste Fund-from which DOE's waste program costs are paid-to pay utilities for on-site storage capacity added after 1998, ability of utilities to store their waste on-site until a repository is operating, and relative costs and safety of the two storage alternatives.